The Frequency of Rheumatic Disease Autoantibodies in Patients with ADAMTS13-Deficient Thrombotic Thrombocytopenia Purpura (TTP).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2090-2090
Author(s):  
Karen K. Swisher ◽  
Qurana F. Lewis ◽  
Judith A. James ◽  
Johanna A. Kremer Hovinga ◽  
Bernhard Lämmle ◽  
...  
Keyword(s):  
Rheumatic Disease ◽  
Plasma Exchange ◽  
Potential Risk ◽  
Lupus Erythematosus ◽  
Autoimmune Disorders ◽  
First Episode ◽  
Adamts13 Activity ◽  
Disease Systemic Lupus Erythematosus ◽  
Increased Risk ◽  
Adamts13 Deficiency

Abstract Patients who have TTP associated with acquired, severe ADAMTS13 deficiency have an autoimmune etiology and therefore may have increased risk for additional autoimmune disorders. The Oklahoma TTP-HUS Registry enrolled 247 consecutive patients with their first episode of clinically diagnosed TTP from 11-13-1995 (the date of our initial ADAMTS13 measurement) to 6-30-2006 for whom plasma exchange treatment was requested; ADAMTS13 activity was measured in 228 (92%) of patients immediately before their first plasma exchange treatment; 42 (18%) patients had ADAMTS13 activity <10%. Three patients were excluded from this analysis because of preexisting systemic rheumatic disease (systemic lupus erythematosus (SLE), 2, Sjogren’s syndrome, 1). To examine the potential risk for development of autoimmune disorders, we measured screening autoantibodies (ANA, dsDNA, Sm, nRNP, Ro, La, ribosomal P, Jo-1, anti-phospholipid (aPL) IgG and IgM) in 34 of the 39 (87%) remaining patients. The median age at initial presentation was 39 years (range 9–71 years); 27 (79%) patients were women; 13 (41%) patients were black. Autoantibodies were measured by indirect immunofluorescence, immunodiffusion, or ELISA. Measurements were performed only once in 16 patients; in 18 patients 2–3 measures were performed over a period of 13 to 126 months. Rheumatic disease autoantibodies TTP patients *1 patient had a maximum titer of >1:3240 in 2 samples; 1 patient developed overt SLE and his titer decreased with treatment. ANA ≥1:40 on at least one occasion 33/34 (97%) ANA ≥1:120 on at least one occasion 29/34 (85%) ANA measured ≥2 times, increasing titer 14/16* (88%) Anti-dsDNA ≥1:30 12/34 (35%) Anti-Ro positive 14/29 (48%) Anti-Sm positive 1/34 (3%) Anti-nRNP positive 1/34 (3%) aPL IgG and/or IgM ≥moderate positive 4/34 (12%) No patients had positive tests for anti-La, anti-Ribo-P, or anti-Jo-1. 23 (68%) of the 34 patients had a positive test for one or more rheumatic disease autoantibodies (dsDNA, nRNP, Ro, La, or moderately positive aPLs). 4 of the 34 patients died during their initial episode; the remaining 30 patients have been followed for a median of 6.4 years (range, 1–11.5 years). During this time only 1 patient has developed clinically evident SLE; no other patients have developed systemic rheumatic diseases. Conclusions: A high prevalence of rheumatic disease-associated autoantibodies were found in a cohort of consecutive patients with TTP associated with acquired severe ADAMTS13 deficiency. The presence of dsDNA and Ro autoantibodies and increasing ANA titers suggest that patients with ADAMTS13-deficientTTP may have a potential risk for developing additional autoimmune disorders such as SLE or Sjogren’s syndromes. [3] These serologic observations support clinical observations that presenting features of TTP and SLE may overlap.

Are Patients Who Have Recovered From ADAMTS13-Deficient Thrombotic Thrombocytopenia Purpura (TTP) at Risk for Developing Systemic Lupus Erythematosus (SLE)?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2519-2519
Author(s):  
Deirdra R. Terrell ◽  
Zayd Al-Nouri ◽  
Judith A. James ◽  
Johanna A. Kremer Hovinga Strebel ◽  
Bernhard Lämmle ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Features ◽  
Lupus Erythematosus ◽  
Conflicts Of Interest ◽  
Population Data ◽  
First Episode ◽  
Adamts13 Activity ◽  
Acr Criteria ◽  
Adamts13 Deficiency

Abstract Abstract 2519 TTP associated with acquired, ADAMTS13-deficiency and SLE are both autoimmune disorders that occur preferentially in young, black women and they have many similar clinical features. TTP may occur in patients previously diagnosed with SLE, or patients may develop SLE following recovery from TTP. In addition, TTP may be quite difficult to distinguish from SLE patients with severe hematologic manifestations. We compared the prevalence of SLE-associated autoantibodies in TTP patients to published population data using 95% confidence intervals (CI). The Oklahoma TTP Registry enrolled 292 consecutive patients with their first episode of clinically diagnosed TTP from 11–13-1995 (date of our initial ADAMTS13 measurement) to 7–31-2009; ADAMTS13 activity was measured in 271 (93%) patients; 64 (24%) patients had ADAMTS13 activity <10%, 63 were evaluated for SLE-associated autoantibodies, including 2 patients with a previous diagnosis of SLE. Serum from the patient's acute initial episode was used for analysis. The prevalence of ANA, anti-dsDNA, anti-Ro, and aPL in TTP patients was significantly higher than published population data; prevalences of anti-nRNP, anti-Sm, and anti-La were not different. Autoantibody TTP (95% CI) Population % ANA  ≥1:40 89% (78%–95%) 0–27%  ≥1:120 56% (42%–68%) 0% Anti-dsDNA  ≥1:30 43% (30%–56%) 3% Anti-Ro  OD>0.350 17% (8%–29%) 3% aPL IgM  ≥20 PL units 15% (7%–26%) 2% Because of the increased prevalence of SLE-associated autoantibodies, we evaluated our TTP patients for the America College of Rheumatology (ACR) criteria for SLE (presence of ≥4 of 11 criteria suggests the diagnosis of lupus); abnormalities associated with any TTP episode were not counted in this evaluation of clinical criteria for SLE. By definition ACR criteria can be fulfilled serially or simultaneously over a lifetime. Evaluations were completed between 6-1-2007 and 5-1-2009 on 38/42 (90%) eligible patients (alive, non-institutionalized, no previous SLE diagnosis) consisting of physical examination, review of available lifetime medical records, and serial laboratory evaluations. Patients have been followed for a median of 8.3 years (range, 1–14 years). During this time, 3 (8%) developed clinically evident SLE requiring treatment 1, 5, and 70 months after their initial TTP episodes. Among the other 35 patients, 3 (8%) have ≥4 SLE classification criteria by medical record review (1 had pre-existing Sjögren's syndrome and receives treatment; 2 have minimal clinical features and are not actively treated for SLE); 9 (24%) have 3 criteria; 16 (42%) have 2 criteria; 6 (16%) have 1 criterion; and 1 (2%) patient has no ACR criteria for SLE. All patients continue to be followed and clinically evaluated for potential intervention. SLE diagnosis is a clinical designation and because of the lack of disease modifying drugs, routine follow-up is standard of care unless the patient is symptomatic. Conclusions: [1] A high prevalence of SLE-associated autoantibodies was present in a cohort of consecutive patients with TTP associated with acquired severe ADAMTS13 deficiency. [2] The presence of anti-dsDNA, anti-Ro, aPL and high titers of ANA suggest that patients with ADAMTS13-deficient TTP may be at risk for developing SLE. [3] During long-term follow-up, 6 (16%) of 38 patients have developed overt SLE or ACR criteria without an established diagnosis of SLE. Careful continuing evaluation following recovery from TTP is important. Disclosures: No relevant conflicts of interest to declare.

Thienopyridine-Associated Thrombotic Thrombocytopenia Purpura: Updated Antibody Results From the SERF-TTP Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 892-892
Author(s):  
Anaadriana Zakarija ◽  
Thanh Ha Luu ◽  
Hau C. Kwaan ◽  
June McKoy ◽  
Ivy Weiss ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Neutralizing Antibodies ◽  
Conflicts Of Interest ◽  
Therapeutic Plasma Exchange ◽  
Severe Thrombocytopenia ◽  
Adamts13 Activity ◽  
Laboratory Findings ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Drug Dependent

Abstract Abstract 892 Background: The thienopyridines, ticlopidine and clopidogrel, have been associated with thrombotic thrombocytopenia purpura (TTP). However, few studies have reported information on antibodies to ADAMTS13 among patients with thienopyridine-associated TTP. We previously reported on two mechanistic pathways of thienopyridine-associated TTP with some overlapping features. Evaluation of ADAMTS13 autoantibodies was undertaken to improve understanding of these syndromes. Methods: Clinical and laboratory findings were evaluated for 30 ticlopidine-, 10 clopidogrel-associated TTP cases, and 54 cases of idiopathic TTP. Results: Among patients with thienopyridine-induced TTP, those with a history of ticlopidine versus clopidogrel use were more likely to present with severe thrombocytopenia (platelet < 20,000) (90% versus 13%), severe ADAMTS13-deficiency (80% versus 0%), and neutralizing antibodies to ADAMTS13 (100% versus 0%), and were less likely to have less than a two week history of thienopyridine exposure (0% versus 50%) (p<0.05 for each comparison). They were also more likely to survive following therapeutic plasma exchange (TPE) (85% versus 50%). 2 patients exposed to clopidogrel later relapsed and had similar characteristics to idiopathic TTP patients with non-deficient ADAMTS13 activity. Conclusion: Ticlopidine causes TTP by a pathway involving a neutralizing autoantibody to ADAMTS13 while clopidogrel causes TTP by an ADAMTS13-independent pathway. Although ADAMTS13 autoantibodies are present in both idiopathic and ticlopidine-associated TTP, spontaneous relapses are not seen in ticlopidine-associaated TTP, suggesting that drug-dependent antibodies are present. Clopidogrel associated TTP is distinct from idiopathic TTP in that ADAMTS13 autoantibodies are absent and response to TPE is poor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals COVID-19 in women with rheumatic disease who are pregnant: Data from the COVID-19 Global Rheumatology Alliance

2021 ◽  
pp. jrheum.210480
Author(s):  
Bonnie L. Bermas ◽  
Milena Gianfrancesco ◽  
Helen L. Tanner ◽  
Andrea M. Seet ◽  
Mathia C. Aguiar ◽  
...  
Keyword(s):  
Rheumatic Disease ◽  
Pregnant Women ◽  
Lupus Erythematosus ◽  
Pregnancy Outcomes ◽  
Supplemental Oxygen ◽  
Increased Risk ◽  
Specific Medication ◽  
Time Of Infection ◽  
Term Births ◽  
Poor Outcomes

Objective To describe coronavirus disease-2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. Methods Since March 2020 the COVID-19 Global Rheumatology Alliance (GRA) has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. Results We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included: rheumatoid arthritis (n=9), systemic lupus erythematosus (n=9), psoriatic/other inflammatory arthritides (n=8) and anti-phospholipid antibody syndrome (n=6). Most had a term birth (16/22), with 3 pre-term births, one termination, one miscarriage and one woman yet to deliver at time of report. A quarter (n=10/39) of pregnant women were hospitalised following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalised); no patient died. The majority did not receive specific medication treatment for their COVID-19 (n=32/39, 82%), seven patients received some combination of anti-malarials, colchicine, anti-IL-1beta, azithromycin, glucocorticoids, and lopinavir/ritonavir. Conclusion Women with rheumatic diseases who were pregnant at the time of COVID-19 had favourable outcomes. These data have limitations due to the small size and methodology, though they provide cautious optimism for pregnancy outcomes for women with rheumatic disease given the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.

Survival and relapse in patients with thrombotic thrombocytopenic purpura

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1500-1511 ◽  
Author(s):  
Johanna A. Kremer Hovinga ◽  
Sara K. Vesely ◽  
Deirdra R. Terrell ◽  
Bernhard Lämmle ◽  
James N. George
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Signs And Symptoms ◽  
Population Based ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Estimated Risk ◽  
Subsequent Relapse ◽  
Organ Dysfunctions

AbstractSurvival of patients with thrombotic thrombocytopenic purpura (TTP) improved dramatically with plasma exchange treatment, revealing risk for relapse. The Oklahoma TTP Registry is a population-based inception cohort of all 376 consecutive patients with an initial episode of clinically diagnosed TTP (defined as microangiopathic hemolytic anemia and thrombocytopenia with or without signs and symptoms of ischemic organ dysfunctions) for whom plasma exchange was requested, 1989 to 2008. Survival was not different between the first and second 10-year periods for all patients (68% and 69%, P = .83) and for patients with idiopathic TTP (83% and 77%, P = .33). ADAMTS13 activity was measured in 261 (93%) of 282 patients since 1995. Survival was not different between patients with ADAMTS13 activity < 10% (47 of 60, 78%) and patients with 10% or more (136 of 201, 68%, P = .11). Among patients with ADAMTS13 activity < 10%, an inhibitor titer of 2 or more Bethesda units/mL was associated with lower survival (P = .05). Relapse rate was greater among survivors with ADAMTS13 activity < 10% (16 of 47, 34%; estimated risk for relapse at 7.5 years, 41%) than among survivors with ADAMTS13 activity of 10% or more (5 of 136, 4%; P < .001). In 41 (93%) of 44 survivors, ADAMTS13 deficiency during remission was not clearly related to subsequent relapse.

Sporadic Bloody Diarrhea-Associated Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) in Adults in Oklahoma: Comparison to Adults with Severe Adamts13 Deficiency and to Children with Typical HUS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1317-1317
Author(s):  
Loan Nguyen ◽  
Charity A. Karpac ◽  
Johanna A. Kremer Hovinga ◽  
Bernhard Lämmle ◽  
Deirdra R. Terrell ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Correct Diagnosis ◽  
Patient Characteristics ◽  
Bloody Diarrhea ◽  
First Episode ◽  
Adamts13 Activity ◽  
E Coli ◽  
Uremic Syndrome ◽  
Adamts13 Deficiency

Abstract The frequency, presenting features and clinical outcomes of sporadic TTP-HUS following a prodrome of bloody diarrhea in adults are not described. The Oklahoma TTP-HUS Registry enrolled 237 consecutive patients over age 18 years with their first episode of clinically diagnosed TTP from 11-13-1995 (the date of our initial ADAMTS13 measurement) to 12-31-2006 for whom plasma exchange treatment (PEX) was requested. ADAMTS13 activity was measured on 218 (92%) patients immediately before their first PEX. 16 (7%) of these 218 patients presented with a prodrome of acute bloody diarrhea. 42 (19%) patients had ADAMTS13 activity <10%. 2 patients who presented with acute bloody diarrhea had ADAMTS13 activity <10%; they are analyzed with the bloody diarrhea patients; ADAMTS13 activity in the remaining 14 patients was 40–100%. Children with typical HUS are not usually treated with PEX and therefore are not all included in the Registry. Data on children were retrieved from the Children’s Hospital of Oklahoma for 2002–2006 to identify all children with typical HUS; 28 children were identified. E. coli O157:H7 infection was identified in 5 adults (of 12 tested) and 19 children (of 25 tested). No source for E. coli O157:H7 infection was identified. There were no case clusters except for one family with 2 affected children. In 2 of the adults with bloody diarrhea, a colectomy was performed before the correct diagnosis was made. Patient characteristics Adults, bloody diarrhea prodrome (n=16) Adults, ADAMTS13 deficiency (n=40) Children, diarrhea prodrome (n=28) * p≤0.05 for adult bloody diarrhea prodrome compared to adult ADAMTS13 deficient patients; ** p≤0.05 for adult bloody diarrhea prodrome compared to children bloody diarrhea prodrome patients; †seizure, stroke, coma, focal abnormalities anytime during the course; ‡most abnormal values on the day of diagnosis ± 7 days; median §defined by ↑ Cr ≥ 0.5 mg/dL x 2 days or Cr ≥4.0 and dialysis. Age (years, median) 58 40* 3.8** Female (%) 80% 81% 64% Race (% white) 94% 53%* 75% Severe neurologic abnormalities† 63% 45% 7%** Platelet count (/μL)‡ 24,000 10,000* 34,000 Hematocrit (%)‡ 22 21 18** LDH (/UL) ‡ 1410 1431 1161 Creatinine (mg/dL)‡ 2.7 1.0* 3.7 Acute renal failure§ 50% 8%* 57% Response to PEX (%) 81% 85% NA Dialysis (%) 31% 3%* 57% Death (30 days) 31% 15% 0%** Relapse (%) 0% (0/10) 38% (13/34)* NA Conclusions: TTP-HUS following bloody diarrhea is an endemic, sporadic disorder among adults that is less common and less familiar than in children. Distinct from children, adults with bloody diarrhea have a higher frequency of severe neurologic abnormalities and death; distinct from adults with severe ADAMTS13 deficiency, adults with bloody diarrhea are primarily white, have a higher frequency of acute renal failure, and have not relapsed. Although the role of PEX in the recovery of adult patients presenting with bloody diarrhea is unclear, PEX may be appropriate initial treatment since the mortality is high, many patients appear to respond, and patients with severe ADAMTS13 deficiency may also present with bloody diarrhea apparently caused by intestinal ischemia.

ADAMTS13 activity in thrombotic thrombocytopenic purpura–hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Sara K. Vesely ◽  
James N. George ◽  
Bernhard Lämmle ◽  
Jan-Dirk Studt ◽  
Lorenzo Alberio ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Outcomes ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Initial Management ◽  
Severe Deficiency ◽  
Uremic Syndrome ◽  
Adamts13 Deficiency

Abstract Initial management of patients with thrombotic thrombocytopenic purpura—hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic criteria, high mortality without plasma exchange treatment, and risks of plasma exchange. Although severe ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) deficiency may be specific for TTP, the role of ADAMTS13 activity measurements for initial management decisions is unknown. ADAMTS13 was measured before beginning plasma exchange treatment in 142 (88%) of 161 consecutive patients with clinically diagnosed TTP-HUS with assignment to 1 of 4 categories: less than 5% (severe deficiency), 5% to 9%, 10% to 25%, and more than 25%. Eighteen (13%) of 142 patients had severe ADAMTS13 deficiency. Among 6 predefined clinical categories (stem cell transplantation, pregnant/postpartum, drug association, bloody diarrhea, additional/alternative disorder, idiopathic), severe deficiency occurred only among pregnant/postpartum (2 of 10) and idiopathic (16 of 48) patients. The presenting features and clinical outcomes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinct from the 32 patients with idiopathic TTPHUS who did not have severe ADAMTS13 deficiency. Many patients in all ADAMTS13 activity categories apparently responded to plasma exchange treatment. Therefore, severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment. (Blood. 2003;102:60-68)

Platelets: Thrombotic Thrombocytopenic Purpura

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 315-334 ◽  
Author(s):  
James N. George ◽  
J. Evan Sadler ◽  
Bernhard Lämmle
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Approach ◽  
Adamts13 Activity ◽  
Extensive Experience ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Adamts13 Deficiency ◽  
And Function ◽  
Von Willebrand

Abstract Abnormalities of plasma von Willebrand factor (VWF) have been recognized to be associated with thrombotic thrombocytopenic purpura (TTP) for over 20 years. Patients with chronic, relapsing TTP have VWF multimers that are larger than normal, similar in size to those secreted by cultured endothelial cells. Recent observations have documented that a deficiency of a VWF-cleaving protease (termed ADAMTS13) may be responsible for the presence of these unusually large VWF multimers. Multiple mutations of the ADAMTS13 gene can result in ADAMTS13 deficiency and cause congenital TTP; autoantibodies neutralizing ADAMTS13 protease activity have been associated with acquired TTP. In Section I, Dr. Evan Sadler reviews the structure, biosynthesis, and function of the ADAMTS13 protease. He describes the mutations that have been identified in congenital TTP and describes the relationship of ADAMTS13 deficiency to the development of both congenital and acquired TTP. Dr. Sadler postulates that the development of TTP may be favored by conditions that combine increased VWF secretion, such as during the later stages of pregnancy, and decreased ADAMTS13 activity. In Section II, Dr. Bernhard Lämmle describes the assay methods for determining ADAMTS13 activity. Understanding the complexity of these methods is essential for understanding the difficulty of assay performance and the interpretation of assay data. Dr. Lämmle describes his extensive experience measuring ADAMTS13 activity in patients with TTP as well as patients with acute thrombocytopenia and severe illnesses not diagnosed as TTP. His data suggest that a severe deficiency of ADAMTS13 activity (&lt; 5%) is a specific feature of TTP. However, he emphasizes that, although severe ADAMTS13 deficiency may be specific for TTP, it may not be sensitive enough to identify all patients who may be appropriately diagnosed as TTP and who may respond to plasma exchange treatment. In Section III, Dr. James George describes the evaluation and management of patients with clinically suspected TTP, as well as adults who may be described as having hemolytic-uremic syndrome (HUS). Dr. George presents a classification of TTP and HUS in children and adults. Appropriate evaluation and management are related to the clinical setting in which the diagnosis is considered. A clinical approach is described for patients in whom the diagnosis of TTP or HUS is considered (1) following bone marrow transplantation, (2) during pregnancy or the postpartum period, (3) in association with drugs which may cause TTP either by an acute immune-mediated toxicity or a dose-related toxicity, (4) following a prodrome of bloody diarrhea, (5) in patients with autoimmune disorders, and (6) in patients with no apparent associated condition who may be considered to have idiopathic TTP. Patients with idiopathic TTP appear to have the greatest frequency of ADAMTS13 deficiency and appear to be at greatest risk for a prolonged clinical course and subsequent relapse. Management with plasma exchange has a high risk of complications. Indications for additional immunosuppressive therapy are described.

Thrombotic Thrombocytopenic Purpura (TTP) and Systemic Lupus Erythematosus (SLE): Distinct but Potentially Overlapping Syndromes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 858-858
Author(s):  
Laura Hunt ◽  
Xiaoning Li ◽  
Judith James ◽  
Deirdra R. Terrell ◽  
Bernhard Lammle ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Lupus Erythematosus ◽  
Immunosuppressive Treatment ◽  
Laboratory Data ◽  
First Episode ◽  
P Value ◽  
Serum Samples ◽  
Sledai Score ◽  
Previous Diagnosis ◽  
Adamts13 Deficiency

Abstract A systematic literature review suggests that SLE and TTP co-exist: we identified 51 articles reporting 87 patients who were diagnosed with both TTP and SLE. SLE was diagnosed prior to TTP in 53 (61%), subsequent to TTP in 11 (13%) and simultaneously with TTP in 23 (26%) patients. However a critical distinction is that TTP is a rapidly fatal disease without plasma exchange (PE) treatment while SLE is typically a more chronic disease with intermittent acute flares and PE is not an essential treatment. Therefore when TTP is suspected in a patient with an established diagnosis of SLE, the relative benefits and risks of PE are difficult to assess, since the diagnosis of TTP may be unclear and PE is a procedure with risk for major complications and death. The Oklahoma TTP-HUS Registry has collected serum samples on 185 of 206 (90%) of prospectively enrolled patients with a clinical diagnosis of TTP or HUS from 11/13/1995 to 12/31/2003; all patients have been followed to the present time. We compared presenting features and clinical outcomes of the first episode of TTP-HUS between the 14 (7%) patients in whom SLE had been previously diagnosed to the 22 patients in whom the diagnosis of TTP was supported by severely deficient (<5%) ADAMTS13. None of the 14 patients with a previous diagnosis of SLE had severe ADAMTS13 deficiency (range 7–100%, median 50%). SLE disease activity as measured by the SLEDAI score ranged from 3–32, median 10, indicating that SLE manifestations were severe in most patients. Only 2 patients had inactive lupus as indicated by a SLEDAI score <4. SLE was not considered at the time of diagnosis of the first episode of TTP in the 22 patients with severe ADAMTS13 deficiency. Only 1/22 patients has been subsequently diagnosed with SLE; at the time of an apparent relapse of TTP he had serositis and positive serologic tests; his ADAMTS13 activity at that time was 30%. This patient’s course documents the potential overlap of these two disorders. SLE-TTP(n=14) TTP (n=22) p-value Median values are presented for continuous data. Laboratory data are most abnormal values at diagnosis of TTP-HUS ±7 days Age (years) 39 39 0.820 Race (% Black) 36% 45% 0.563 Gender (% female) 100% 82% 0.140 Obesity (BMI ≥ 30 kg/m²) 14% 55% 0.016 Severe neurologic abnormalities 71% 45% 0.126 Platelet count 21 9 0.010 Hematocrit 22 21 0.660 LDH 707 1431 0.043 Acute renal failure 64% 5% <0.001 Response to PE 36% 86% 0.003 Death 64% 23% 0.018 Relapse in 30 day survivors 0% 44% 0.031 Although the demographic (age, race, gender) and some presenting clinical features of patients with SLE and a clinical diagnosis of TTP-HUS were not different from patients with TTP and severe ADAMTS13 deficiency, other presenting features and the outcomes were different. Response to PE was poor, all cause mortality was high, and relapses of TTP have not occurred in patients with a previous diagnosis of SLE. These differences suggest that these 2 groups of patients in our Registry are distinct. Therefore in patients with an established diagnosis of SLE in whom the additional diagnosis of TTP-HUS is considered, more intensive immunosuppressive treatment for SLE is appropriate initial management in addition to considering the relative benefits and risks of PE.

Thrombotic Thrombocytopenic Purpura At the Cleveland Clinic 2000–2012: Review of 100 Cases and Identification of Prognostic Factors

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3325-3325
Author(s):  
Shruti Chaturvedi ◽  
Desiree Carcioppolo ◽  
Li Zhang ◽  
Keith R. McCrae
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Cleveland Clinic ◽  
Neurological Symptoms ◽  
First Episode ◽  
Refractory Disease ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura

Abstract Abstract 3325 BACKGROUND AND OBJECTIVE: The advent of plasma exchange has led to a dramatic improvement in the survival of patients with Thrombotic Thrombocytopenic Purpura (TTP). However 10–20% of patients do not respond to plasma exchange and up to a third suffer relapses. Recent studies suggest that Rituximab as an adjunct to plasma exchange and corticosteroids may be effective in refractory or relapsing disease, although clinical factors that identify patients at high risk for poor outcomes have not been clearly defined. This concern prompted a retrospective review of all patients with TTP treated at the Cleveland Clinic over the last 12 years in an attempt to identify factors associated with poor prognosis. Records from all patients were reviewed from the date of initial presentation until at least two years afterwards to determine the incidence of refractory disease and relapse. STUDY AND METHODS: A total of 284 patients who were diagnosed with a first episode of thrombotic microangiopathy at the Cleveland Clinic from January 2000 to March 2012 were identified. Records from these patients were reviewed and individuals with other explanations for thrombocytopenia and hemolytic anemia such as DIC, hypertensive crisis or HELLP were excluded. One hundred patients were included in the final analysis. Fischer exact test and t- test were used to compare variables. A p value of <0.05 was considered significant. RESULTS: Of the 100 patients with TTP, 73% were female, with an age range of 16 to 79 years (median 49 years). Fifty percent of patients were Caucasian, 45% African American and 2% Hispanic. Sixty seven percent of cases occurred without predisposing conditions while 12% were associated with autoimmune disease (6 with SLE, 2 with rheumatoid arthritis, one with SLE and rheumatoid arthritis, and one each with Sjogren's syndrome, dermatomyositis and mixed connective tissue disorder), 8% with pregnancy or the postpartum state, 6% each with cancer and solid organ transplantation and 2% each with bone marrow and stem cell transplant. ADAMTS13 activity was tested in 57% of cases of which 36 (63%) had <5% and 21 (37%) had 8% to 56% activity, respectively. All patients were treated with plasma exchange, and all but 17 received corticosteroids, while some received additional therapies including vincristine (10), rituximab (15) and splenectomy (7) for refractory disease. Mortality after a first episode of TTP was 8%, while 13% of patients had exacerbations (within 30 days) and 18% had relapses (11 patients had a single relapse, 6 patients had 2 relapses and 1 had three relapses). Non survivors were older (p=0.042) with this association particularly striking for patients greater than age 60 (OR 8.75, 95% CI 2.32–33.01, p=0.002). Non-survivors also presented more frequently with severe neurological symptoms including obtundation, focal deficits and seizures (p=0.001). A higher LDH level after 1 or 2 cycles of plasma exchange, i.e. LDH on day 3, 4 or 5 of admission was also strongly associated with mortality (p<0.01) as well as with prolonged duration of plasma exchange. ADAMTS13 activity and levels of inhibitory anti-ADAMTS13 antibodies were comparable between survivors and non-survivors. However, undetectable ADAMTS13 levels were associated with a lower incidence of adverse renal outcomes including need for dialysis during the acute episode (p=0.007) and the development of chronic kidney disease (p=0.033) and/or end stage renal disease at 2 years (p=0.015). CONCLUSION: The most significant independent variables predicting death in TTP were increasing age, especially age>60, severe neurological symptoms at presentation and a persistently high LDH level the second day after diagnosis and initiation of plasma exchange. These variables could be used to identify patients who would benefit from close monitoring and potentially from early institution of adjunctive therapy. Treatment of high risk patients in this manner could limit the duration of plasma exchange, improve outcomes, and decrease associated morbidity and costs. Disclosures: No relevant conflicts of interest to declare.

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