Idiopathic Thrombotic Thrombocytopenic Purpura Research Articles

Analysis of Prognosis and Therapeutic Effect of Patients with Thrombotic Thrombocytopenic Purpura

To summarize the features of clinical and laboratory parameters of thrombotic thrombocytopenic purpura (TTP), and to analyze the factors affecting the prognosis and therapeutic effect during the acute phase of the disease. The etiology, clinical features, laboratory parameters, treatment regimens and other data of 59 TTP patients admitted to Hunan Provincial People's Hospital were retrospectively analyzed. And the differences of each variable between the death group and the survival group were compared, the correlations between each variable and prognosis, as well as the therapeutic effect of the acute phase patients were analyzed. Among the 59 cases of TTP, one 4-year-old boy was inherited TTP, the other 58 cases were acquired TTP (39 cases were idiopathic TTP and 19 were secondary TTP), including 27 males and 31 females, with a median age of 54 (11-84) years old. 36 patients were tested for von Willebrand factor cleaving protease (ADAMTS13) activity, and 34 patients (94.44%) had decreased ADAMTS13 activity. There was a statistical difference in the activity of ADAMTS13 between idiopathic and secondary TTP patients (P<0.001). There were statistical differences in factors such as age (64 vs 51 years), ALT/AST ratio (0.61 vs 0.36), therapeutic plasma exchange (TPE) times (3 times vs 8 times), and TPE duration (3 d vs 9 d) between the death and survival groups. Multivariate analysis showed that total times of TPE (OR=5.175,95%CI: 1.169-22.914, P=0.030), ALT/AST ratio (OR=4.387, 95%CI: 1.019-18.891, P=0.047) were associated with mortality. COX regression analysis showed that degree of neuropsychiatric disorder (HR=0.200, 95%CI: 0.084-0.474, P<0.001), days from onset to initiation of TPE (HR=0.288, 95%CI: 0.114-0.726, P=0.008), treatment regimen (HR=0.336, 95%CI: 0.125-0.902, P=0.030) were associated with platelet recovery and therapeutic effect in the acute phase of the patients. TTP patients with high ALT/AST ratio have a higher mortality rate. Patients with enough times and full course of TPE have lower mortality rate. Poor therapeutic effect were found in TTP patients with severe neuropsychiatric disorders, delayed diagnosis and treatment, and who added rituximab when TPE was ineffective.

Adult idiopathic thrombotic thrombocytopenic purpura therapeutic modalities and outcome

Background Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disease that results in fatality if not treated. The studies on TTP are scarce; most of them have small numbers of patients. Since not enough data on Egyptian patients with TTP can be found in the literature, we carried out this retrospective study to define the therapeutic modalities and outcome of these patients. Patients and methods We studied the records of patients clinically diagnosed with TTP from 2006 to 2020. Twenty-nine patients were diagnosed with TTP. However, full records were available only for 22 patients. The primary outcome of the study was the 1-year survival. Other outcomes were the factors on which the survival seemed to depend on such as age, platelet count, lactate dehydrogenase (LDH), serum creatinine, hemoglobin, reticulocytic %, plasma volume exchange (PVE), days to start of treatment, and indirect bilirubin. Results Platelet count change was negatively correlated with both the number of plasma exchange sessions and the days to start of treatment, but it was positively correlated with the volume of plasma exchange. Univariate analysis identified factors associated with better survival of the patients: LDH, reticulocytic percent, days to start of treatment, serum creatinine, PVE, and hemoglobin level. The multivariate analysis revealed that the independent factors affecting the survival were LDH, reticulocytic percent, hemoglobin level, and age. Conclusion Early suspicion and intervention with therapeutic plasma exchange for TTP are associated with better outcomes in these patients. One and a half PVE is associated with better response than 1 PVE.

ADAMS-TS13 Inhibitor Level and Risk of Relapse in Acquired Idiopathic Thrombotic Thrombocytopenic Purpura

▪Introduction:Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy due to reduced activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13). This disorder can be due to a congenital deficiency state or be acquired (immune TTP (iTTP)) due to an antibody which either inhibits or causes clearance of ADAMTS13.The aim of our study was to determine whether ADAMTS13 inhibitor titer at initial presentation could serve as a predictor of refractory disease and relapse in iTTP. We also measured clinical outcomes across different gender and racial subgroups.Methods:The United States Thrombotic Microangiopathy (USTMA) iTTP registry was used to extract patient information for two academic institutions in Eastern North Carolina.Descriptive statistics were used to analyze the data. The first iTTP episode recorded in the data base was used as the index episode. All patients included in the final analysis had an ADAMTS13 activity of <10%. An inhibitor level of 5 Bethesda units was arbitrarily chosen as the cutoff between low (<5) and high (>/5) inhibitor level. Response time was defined as the number of days of plasma exchange (PEX) required to achieve a platelet count of 150,000 for two consecutive days. Relapse was defined as occurrence of a new episode of iTTP 30 days after achievement of response. Refractory disease was defined as persistence of thrombocytopenia or absence of a sustained platelet count increment or platelet counts of < 50,000 despite 4-7 days of plasma exchanges and steroid treatment. Rituximab resistance was defined as lack of platelet recovery to more than 150,000 within 11 to 14 days of administration of the first dose of Rituximab.Results:A total of 161 patients with iTTP were identified. Ten patients had ADAMTS13 activity >10% and 15 patients did not have a reported inhibitor level. These subjects were not included in the final analysis.The cohort had 28% male (n =38/136) and 72% (n=98/136) female patients. There were more African American patients 73% (n=99/136) than Caucasians 24% (n=32/136). There were also 2 Hispanic, 1 Native American and 2 patients with unidentified race.Median ADAMTS3 inhibitor titer was 1.05 (Range 0-87). Forty three patients with ADAMTS13 activity <10 % had an inhibitor level of 0 (i.e undetectable).They were included in the low inhibitor group.Overall, 88% patients (n=120/136) had low inhibitor level and only 12% (n=16/136) had a high inhibitor. Thirteen percent females (n=13/98) and 8% (n=3/38) males had a high inhibitor level (p=0.387). Fourteen percent (n=14/99) African Americans and 6 % (n=2/32) Caucasians had a high inhibitor, p=0.23.In the low inhibitor group 30% (n=36/120) patients suffered at least one episode of relapse whereas 31% (n=5/16) had relapsed in the high inhibitor group.The median time to response was 6 days (range 1-76) in the low inhibitor group and 7 days (range 4-20) in the high inhibitor group (p=0.61). While looking at the various subgroups, median time to response for males was 6 days (range 4-21), females 6 days (range 1-76) , African Americans 6 days (range 3-29) , and Caucasians 6 days (range 1-76).The frequency of refractory disease was 31 % (n=5/16) in the high inhibitor group and 29% (n=34/119) in the low inhibitor group. At the time of enrollment in the registry, Rituximab was not a part of first line therapy. Only 26 out of 136 patients had received Rituximab. In the low inhibitor group 5 patients displayed Rituximab resistance whereas there were no patients in the high inhibitor group with Rituximab resistance.Conclusion:When evaluating patients presenting with iTTP in two centers in North Carolina, no correlation was found between a high inhibitor levels of >/ 5 Bethesda units and risk of relapse or refractory disease. A larger study is needed to evaluate this further. DisclosuresNo relevant conflicts of interest to declare.

Idiopathic Thrombotic Microangiopathy with ChAdOx1 nCov-19 Vaccination in a Middle Aged Male: A Clinical Challenge in the Covid Era

Thrombotic thrombocytopenic purpura (TTP) is defined as thrombotic microangiopathy occurring in the context of severe ADAMTS13 deficiency (<10%) which is a normal enzyme in plasma that cleaves large forms of von Willebrand factor into smaller functional subunits. We report a case of a middle aged male with de novo iTTP ( idiopathic thrombotic thrombocytopenic purpura) after vaccination with ChAdOx1 nCov-19. He presented with severe abdominal pain, increased bruising, hematuria along with episodes of transient ischemic attacks, 5 days from the first dose of the antiCOVID-19 vaccine. Laboratory data revealed a very severe ADAMTS13 deficiency, however, autoantibody titer could not be measured due to the failure of refrigerating facility in our reference laboratory. Patient was successfully treated with serial plasma exchange and immunosuppression with steroids and rituximab.

Idiopathic TTP in the Middle East: Epidemiology and clinical outcomes in infection associated episodes

IntroductionLiterature on epidemiology of thrombotic thrombocytopenic purpura (TTP) in the Middle East is scarce. Materials and methodsWe prospectively examined the association between infection and clinical outcomes in 44 patients with idiopathic TTP, with severely deficient ADAMTS13. We also investigated seasonality of the disease, hoping to better understand the epidemiology of idiopathic TTP. ResultsSummer demonstrated significantly lower incidence for idiopathic TTP, compared with other seasons P = 0.0003. Fourteen patients had 15 episodes with a suspected concomitant infection. Five initial episodes were triggered by an infection (33.3 %), all presenting in winter, six episodes were associated with an exacerbation (40 %) and infection triggered a relapse in the other four episodes (26.7 %), with 2 episodes presenting in winter.TTP associated infections included: central line infection, urinary tract infection and post-operative infection. One patient had respiratory tract infection, on both his initial and relapsing episodes. Refractoriness to treatment was demonstrated in 4 patients (28.6 %) and it was associated with dental abscess (one patient), septic shock (one patient) and Mycoplasma pneumonia (2 patients). All 4 patients had markedly elevated CRP values with a median of 335 mg/L. ConclusionMost of the infection associated episodes developed in winter (77.8 %).In patients with idiopathic TTP refractory to conventional treatment, infection should be seriously considered as an additional contributing factor for their initial and /or recurrent episodes, particularly when CRP is markedly elevated.

Clinical presentation in thrombotic thrombocytopenic purpura: Real-world data from two Mexican institutions.

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease that can be fatal if not treated early. We aimed to describe the clinical characteristics of Mexican patients with idiopathic TTP. We conducted a retrospective study, including all adult patients diagnosed with idiopathic TTP from 2011 to 2017 in two Mexican centers. We further compared our results with the published literature. Twenty patients were included; 70% were female, with a median age of 38.5 years at diagnosis (range 16-63). The median time from onset of symptoms to hospital admission was 1.5 days (range 0-16). Most patients (85%) presented with at least one systemic manifestation at admission (including fever) and 90% had neurological symptoms, most of them major (70%) including loss of consciousness, transient focal abnormalities, headache, and confusion. Only one patient (5%) had the classical pentad at the time of admission. Kidney failure was present in 25% of patients and hemorrhagic symptoms in 60%. Digestive and cardiorespiratory symptoms were less common (45% and 15%, respectively). Median platelet count and lactate dehydrogenase were 10 500/μL and 1319 IU/L, respectively. Eighty percent of patients achieved remission following treatment. Patients admitted within the first 48 hours (after the onset of symptoms) tended to have better overall survival. Clinical presentation in Mexican TTP patients is similar to that in other countries. Early admission and a high suspicion for the disease will avoid delays in the initial work-up and initiation of therapy, further improving prognosis.

Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura.

The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying deficiency of the ADAMTS13 protease is caused by autoantibodies, predominantly of the IgG isotype. Certain HLA-DR-DQ haplotypes were associated with the risk of developing TTP. To investigate the development of the ADAMTS13-specific antibody response during the course of the disease, we analyzed the concentration, subclass distribution, and inhibitory potential of anti-ADAMTS13 IgG autoantibodies in samples of TTP patients drawn during the first acute phase, in remission, and during relapse. Additionally, we compared the anti-ADAMTS13 IgG levels between patients carrying and not carrying risk and protective HLA-DR-DQ haplotypes. We determined the anti-ADAMTS13 IgG concentration and subclass distribution in 101 antibody-positive samples of 81 acquired TTP patients by ELISA methods. The presence and semi-quantitative amount of anti-ADAMTS13 inhibitors were determined in 97 of 100 deficient samples, and the specific inhibitory potential of anti-ADAMTS13 autoantibodies was determined in 49 selected samples, by mixing ADAMTS13-activity assays. HLA-DR-DQ typing and haplotype prediction were performed in 70 of the above patients. We found that IgG1 and IgG4 were the predominant subclasses, present in almost all samples. While IgG1 was the dominant subclass in almost half of the samples taken during the first acute episode, IgG4 was dominant in all samples taken during or following a relapse. The inhibitory potential of the samples correlated with levels of the IgG4 subclass. Anti-ADAMTS13 antibodies of IgG4-dominant samples had higher specific inhibitory potentials than IgG1-dominant samples, independently of disease stage. Interestingly, we found that patients carrying the protective DR7-DQ2 and DR13-DQ6 haplotypes had higher anti-ADAMTS13 IgG levels. Our results indicate that IgG4 becomes the dominant subtype at some point of the disease course, apparently before the first relapse, parallel to the increase in inhibitory potential of the anti-ADAMTS13 autoantibodies. Furthermore, we found an association between the genetic background and the antibody response in TTP.

Implementation of a rapid assay of ADAMTS13 activity was associated with improved 30-day survival rate in patients with acquired primary thrombotic thrombocytopenic purpura who received platelet transfusions.

Platelet (PLT) transfusions are probably harmful in patients with acquired idiopathic thrombotic thrombocytopenic purpura (aTTP). Introduction of a rapid assay for ADAMTS13 activity should reduce the time to definite diagnosis of aTTP, reduce the amount of inappropriately transfused PLT concentrates, and improve mortality and morbidity. We selected 265 aTTP patients with severe ADAMTS13 deficiency. Of these, 91 patients were diagnosed by March 2005 (Period 1), when ADAMTS13 activity was measured by von Willebrand factor multimer assay, which took 4 to 7 days until the result was reported. An additional 174 patients were diagnosed after April 2005 (Period 2), when the activity was measured by a chromogenic enzyme-linked immunosorbent assay, which took 1 to 2 days. We found no significant differences in 30-day survival rate between the two periods. Overall, 48 patients received PLT transfusions. Mortality was slightly greater between patients with (22.9%) versus without PLT transfusion (17.7%), but not significant. In Period 1, Cox proportional hazards regression analysis showed that older age (≥60 years) and PLT transfusion administration were independent factors associated with higher risks of 30-day mortality. In contrast, in Period 2, lower Rose-Eldor TTP severity score and use of plasma exchange and corticosteroid therapy were independent factors associated with higher survival rates while nonadministration of PLT transfusions was not. Our results indicate that PLT transfusions are harmful for aTTP patients when the definite diagnosis of severe ADAMTS13 deficiency is delayed. If it can be done as soon as possible, PLT transfusions for severe bleeding or surgical interventions might be allowed with subsequent plasmapheresis.

Acquired Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab

Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition who presented with left-sided weakness and seizure-like activity preceded by headache and easy bruising. She did not achieve optimal response to plasma exchange, corticosteroids, rituximab, and vincristine. We initiated treatment with eculizumab, following which she had durable remission that continued for 30 months after discontinuation of the drug. We later found that our patient has homozygous deletion in two closely related genes, complement factor H–related 1 and complement factor H–related 3.

Evaluating the impact of the ABO blood group on the clinical outcome of thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency.

Thrombotic thrombocytopenic purpura (TTP) is caused by the decrease of ADAMTS13, leading to the accumulation of ultra large von Willebrand factor (ULVWF). It was proposed that the distribution of blood group O among TTP patients may be potentially lower than expected because of the lower levels of VWF. The aim of this study was to explore the relationship between various blood groups and the clinical outcome in TTP. Thirty-three patients with TTP with severe ADAMTS13 deficiency were studied. Data on blood group, relapse, number of plasma exchange sessions, replacement fluid and mortality were analysed. Mortality rate was 15·2% and it was not impacted by blood group. The distribution of group O among patients with idiopathic TTP was lower (12%) than expected (30%). Patients with blood group O required more sessions to achieve remission than did those with group B (P = 0·02). Cryo-supernatant was used in three refractory patients with group O, who failed to respond to fresh-frozen plasma and complete remission was achieved. The overall number of relapsing episodes was 7 of 33 (21·2%), and it was not impacted by blood group. Although blood group O appeared to provide protection against TTP, more sessions were required to achieve remission. Cryo-supernatant improved the clinical outcome in refractory patients with group O. Future studies may be warranted to determine whether higher baseline VWF can be a trigger for TTP, or can confer protection by competing with a newly secreted ULVWF for platelet binding.

Risk Factors Associated with Multiple End-Organ Damage in Idiopathic Thrombotic Thrombocytopenic Purpura (TTP) Patients

Introduction: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare hematological disorder caused by deficiency of ADAMTS13 activity and subsequent development of vWF-platelets-rich microthrombi leading to tissue ischemia and organ dysfunction. Standard treatment consists of daily plasma exchange (PEX) to remove the autoantibodies and replenishes ADAMTS13 activity and immunosuppressive therapy for patients with autoimmune process. Recent publication showed that caplacizumab, an anti-vWF humanized nanobody which inhibits the interaction between vWF multimers and platelets, can be used together with PEX to reduce time to platelet normalization but not risk of relapse when compared to placebo. However, incorporate caplacizumab with PEX in high risk TTP patients maybe even more important to reduce long-term organ damage. Therefore, we performed a retrospective single center analysis of TTP patients to identify the incidence and risk factors associated with end-organ damage. Method: Sixteen adult patients with idiopathic TTP were identified from January 2005 through December 2015. Idiopathic TTP was defined as thrombotic microangiopathy with an ADAMTS13 ≤10%. Cardiac involvement was defined as an increased Troponin I (TnI) level &gt;0.1µg L-1. Renal involvement was defined as serum creatinine &gt;1.30mg/dL. Of note, all the 16 patients had normal baseline renal function. Neurological involvement was defined as documentation of confusion, headaches, seizure, aphasia and syncope. The time to a platelet response was defined as a platelet count that was ≥150,000/mm3 for at least 48 hours. All patients were treated with PEX, corticosteroids, ± rituximab. Results: The mean (range) age was 48 (23 to 78) and the female: male ratio was 12:4. All (16) patients had end-organ involvements: 16 (100%) neurological, 6 (37.5%) renal, and 4 (25%) cardiac. Seven patients (43.75%) had single organ involvement (Group one), 9 patients (56.25%) had two or three organ involvement (Group two). The mean age for Group one was 44 as compared to 51 for Group two. The mean LDH level on admission was 987 IU/L (range: 417-1,289 IU/L) for Group one as compared to 1,715 IU/L (range: 336-4,455 IU/L) for Group two (p value: 0.06). The mean platelet count on admission was 20 k/µL for Group one as compared to 18 k/µL for Group two. The mean hemoglobin level on admission was 7.5g/dL (range: 5.3-8.6g/dL) for Group one as compared to 8.78g/dL (range: 8.1-10.5g/dL) for Group two. The median time to a platelet response was 5 days in this study population. Conclusions: Our study showed that more than 50% of TTP patients presented with multi-organ involvement. Very high LDH at initial presentation prior to PEX was identified as a probable single risk factor associated with multi-organ involvement. Prompt arrest of vWF-mediated platelet aggregation with agents such as calpalacizumab in TTP patients could prevent or minimize early irreversible end-organ damage due to tissue ischemia. Identifying risk factors for severe end-organ involvement will be important to study the potential benefit of incorporating calpalacizumab into TTP treatment. Further study on the risk factors for end-organ involvements in TTP patients and their long-term outcome at a multi-center level and with a larger patient population is warranted. Disclosures No relevant conflicts of interest to declare.

Thrombotic Thrombocytopenic Purpura with Cardiac Involvement after an Allergic Reaction to Turmeric and Cumin: A Case Report

Background: Cuminum cyminum (Cumin) and Curcuma longa (Turmeric) are plant derived spices which are commonly used as a part of everyday recipes in variety of cuisines. They are known causes of platelet dysfunction but Thrombotic thrombocytopenic purpura (TTP) following their consumption has never been reported in the literature. Primary cardiac involvement in TTP is a rare but fatal complication and may present as AMI, heart failure or arrhythmias. Case Report: We report a case of a 46-year-old male who presented with features of spontaneous bleeding following consumption of Cumin and Turmeric. Laboratory investigations revealed hemolytic anemia, marked thrombocytopenia and blood smear showed schistocytes. In addition, cardiac involvement was noted as per changes seen on the EKG and markedly elevated Troponin I level. At this stage TTP was diagnosed which was subsequently confirmed by reduced ADAMTS13 activity level of <10%. He was successfully treated with Plasma Exchange (PEX) and Rituximab. PEX was complicated by 5 episodes of non-sustained Ventricular Tachycardia which was managed by Amiodarone. Conclusion: Although the link between ADAMTS13 deficiency and idiopathic TTP has been well-established, the role of Cumin and Turmeric in the pathogenesis of TTP is not yet well clarified. We speculate that the acquired ADAMTS13 deficiency might have been triggered by those Spices. Myocardial injury is underdiagnosed in patients with TTP and is associated with higher mortality. Hence, patients diagnosed with TTP should be monitored for adverse cardiac events due to the high incidence of new AMI, arrhythmias and congestive heart failure.

The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura

The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA), responsible for antigen presentation, play an important role in the development of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a protein tyrosine phosphatase important in lymphocyte activation, predisposes to a number of autoimmune diseases. We determined the HLA-DRB1-DQB1 haplotypes and the PTPN22 c.1858C>T genotypes in 75 patients with acquired idiopathic TTP and in healthy controls, in order to assess the role of these genetic factors and their interactions in the susceptibility to TTP. We found that the carrier frequencies of the DRB1∗11-DQB1∗03 and DRB1∗15-DQB1∗06 haplotypes were higher, while those of the DRB1∗07-DQB1∗02 and DRB1∗13-DQB1∗06 haplotypes were lower in TTP patients. There was no difference in the overall frequency of the PTPN22 c.1858T allele between TTP patients and controls. In conclusion, we identified four HLA-DRB1-DQB1 haplotypes associated with an increased (DRB1∗11-DQB1∗03 and DRB1∗15-DQB1∗06) or a decreased (DRB1∗07-DQB1∗02 and DRB1∗13-DQB1∗06) susceptibility to acquired idiopathic TTP.

Adenocarcinoma of the Lung Presenting as Thrombotic Thrombocytopenic Purpura

SESSION TITLE: Student/Resident Case Report Poster - Lung Cancer II SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Thrombotic microangiopathy may be the first manifestation of solid tumors such as lung cancer. Thrombotic thrombocytopenic purpura (TTP) includes the pentad of thrombocytopenia, hemolytic anemia, fever, neurologic abnormalities, and renal disease. We present a case of acute TTP as the first presentation of lung cancer. Prompt recognition and management resulted in a good outcome. CASE PRESENTATION: A 56-year-old African American male with no significant PMH was transferred to our center with an altered mental status. The patient reports that he did not have recollection of the events surrounding his admission and he was having difficulty answering questions appropriately. Physical examination was normal. CBC showed normal leukocytes count, anemia, and platelets count of 16,000. Peripheral smear showed reticulocytosis and schistocytes. Chemistry revealed a mildly elevated creatinine, indirect bilirubin and AST. LDH was elevated. Routine chest X-ray revealed a 3 cm left upper lobe lung mass, a finding confirmed with a chest CT. Mass biopsy showed a poorly differentiated adenocarcinoma of the lung. He was started on plasmapheresis which resulted in short-lived improvement. He underwent a left upper lobe lobectomy, after which, he went into complete remission. DISCUSSION: Cancer related thrombocytopenia can result either from bone marrow metastasis or as a paraneoplastic process. TTP, commonly affects adults, is a life-threatening disseminated thrombotic microangiopathy. Patients rarely present with the pentad of TTP, and recognition of atypical cases and prompt management (plasmapheresis/treatment of underlying condition) is a key factor in improved survival. The presence of a primary malignancy is an essential concern in the differential diagnosis of TTP, particularly in patients with refractoriness to first-line therapy with plasmaperesis; however, sometimes the malignancy is not clinically obvious (as in our case), leading to an initial diagnosis of idiopathic TTP and subsequent plasmapheresis treatment. The treatment of the underlying malignancy may be the best therapeutic decision in paraneoplastic TTP given its poor response to standard treatments (as in our case). CONCLUSIONS: TTP is a medical emergency that is almost always fatal if exchange plasmapheresis is not initiated early. This case report reminds clinicians that TTP may be an atypical presentation of lung cancer and occult malignancy should always be kept in consideration in patients with thrombocytopenia of uncertain etiology. Reference #1: M. Khasraw, H. Faraj, and A. Sheikha. Thrombocytopenia in solid tumors. European Journal of Clinical and Medical Oncology, vol. 2, no. 2, pp. 89-92, 2010 Reference #2: Sevinc A, Kalender ME, Pehlivan Y, Sari I, Camci C.Thrombotic Thrombocytopenic Purpura and Bone Marrow Necrosis as the Initial Presentation of Lung Cancer. Clin Appl Thromb Hemost. 2007 Oct;13(4):449-52 Reference #3: Gastineau DA, Cancer-related TTP and considerations of plasma exchange. Oncology, 2011 Sep;25(10):924, 926 DISCLOSURE: The following authors have nothing to disclose: Ahmed Dirweesh No Product/Research Disclosure Information

Autoimmune hemolytic anemia presenting concurrently with thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening syndrome typically characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Both genetic and idiopathic TTP are caused by deficient activity of the serine protease ADAMTS-13, allowing its normal substrate, von Willebrand factor, to polymerize and bind platelets under high sheer conditions. Autoimmune TTP is typically treated by plasmapheresis and corticosteroids. Here, we describe a 69-year-old patient presenting with thrombopenia comorbid with "warm" autoimmune hemolytic anemia (WAIHA). Treatment with steroids and plasma exchange initiated at the beginning and patient acquired a clinical as well as biological response. Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition typically (but not always) associated with autoimmune or genetic inactivation of the protease ADAMTS-13, for which consistently effective therapeutic interventions remain elusive.

Idiopathic thrombotic thrombocytopenic purpura: strongest risk factor for relapse from remission is having had a relapse.

Thrombotic thrombocytopenic purpura (TTP) is a rare, episodic clinical syndrome involving the production of thrombi in the microvasculature accompanied by thrombocytopenia and symptoms of organ ischemia. Idiopathic TTP develops when a patient produces antibodies that react with the protease ADAMTS13. The course after an episode is unpredictable; patients may relapse frequently or never. There is no laboratory value that can reliably predict potential relapse. To assess diagnostic and predictive values for risk of relapse, plasma samples from 27 patients with idiopathic TTP in remission were analyzed for anti-ADAMTS13 immunoglobulin (Ig)G, ADAMTS13 activity, and ADAMTS13 inhibitor titer. Patients were recruited at the Department of Hematology at the University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. Anti-ADAMTS13 IgG was detected in 12 patients (44%); their median level of ADAMTS13 activity was nondetectable. Patients with anti-ADAMTS13 IgG had a median number of three previous relapses, whereas the 15 patients without presence of IgG (56%) had a median number of one previous relapse (p<0.001; Mann-Whitney Utest). The concentration of free anti-ADAMTS13 IgG and the levels measuring inhibitory activity (Bethesda unit) were positively correlated. A subgroup of TTP patients in remission with anti-ADAMTS13 IgG and nondetectable ADAMTS13 activity showed an increased risk for relapsing disease as demonstrated by their number of past relapses. The positive correlation we observed between anti-ADAMTS13 IgG and inhibitor levels supports the theory of ADAMTS13 inhibition as the crucial mechanism causing severe deficiency in ADAMTS13 activity in TTP.

Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity <10%). We aimed to investigate the association between mechanisms for ADAMTS13 deficiency and the epidemiology and pathophysiology of thrombotic thrombocytopenic purpura at initial presentation. Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with mutations of the ADAMTS13 gene. Idiopathic thrombotic thrombocytopenic purpura were mainly autoimmune (345 [91%] cases), whereas non-idiopathic diseases were heterogeneous, including a high rate of unexplained mechanisms for ADAMTS13 deficiency (133 [34%] cases). Obstetrical thrombotic thrombocytopenic purpura cases (n=62) were specifically remarkable because of the high rate of patients with Upshaw-Schulman syndrome (21 [34%] patients). Our study shows that thrombotic thrombocytopenic purpura is a heterogeneous syndrome, and that features of the disease at presentation are strongly associated with the mechanisms of ADAMTS13 deficiency. In addition to mechanistic insight, our findings could have implications for the initial therapeutic management of patients with this disorder. Assistance Publique-Hôpitaux de Paris.

Autoimmune hemolytic anemia presenting concurrently with thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening syndrome typically characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Both genetic and idiopathic TTP are caused by deficient activity of the serine protease ADAMTS-13, allowing its normal substrate, von Willebrand factor, to polymerize and bind platelets under high sheer conditions. Autoimmune TTP is typically treated by plasmapheresis and corticosteroids. Here, we describe a 69-year-old patient presenting with thrombopenia comorbid with "warm" autoimmune hemolytic anemia (WAIHA). Treatment with steroids and plasma exchange initiated at the beginning and patient acquired a clinical as well as biological response. Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition typically (but not always) associated with autoimmune or genetic inactivation of the protease ADAMTS-13, for which consistently effective therapeutic interventions remain elusive.

Thrombotic thrombocytopenic purpura - analysis of clinical features, laboratory characteristics and therapeutic outcomeof 24 patients treated at a Tertiary Care Center in Saudi Arabia

Objective:Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patientsMethods:This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC).Results:Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR.Conclusion:TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities..

Therapeutic dilemma in the management of a patient with the clinical picture of TTP and severe B12 deficiency

BackgroundIdiopathic thrombotic thrombocytopenic purpura (TTP) is a rare hematological emergency characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal injury, and fever that is invariably fatal if left untreated. Prompt intervention with plasma exchange minimizes mortality and is the cornerstone of therapy. Rare reports have described “pseudo-TTP” driven by extreme hematologic abnormalities resulting from deficiency of vitamin B12. Distinguishing between these entities can pose a diagnostic and therapeutic challenge.Case presentationA 77 year old female presented with altered mental status, renal insufficiency, thrombocytopenia and evidence of microangiopathic hemolytic anemia, suggesting TTP. Workup demonstrated macrocytosis and reticulocytopenia, and B12 level was unmeasurably low. Other elements of her clinical presentation, including volume loss and bleeding suggested a multifactorial pathogenesis could be contributing to her laboratory abnormalities, reducing the likelihood that she had TTP. The risks and benefits of treating aggressively with therapeutic plasma exchange (TPE) for TTP were considered given the diagnostic possibilities. The patient received TPE initially, with rapid de-escalation after her clinical response suggested “pseudo-TTP” from B12 deficiency was the driving the process. B12 supplementation corrected her hematologic abnormalities and she remains well two years after presenting.ConclusionsTTP is a rare condition with fatal consequences if left untreated. Guidelines recommend TPE even if there is uncertainty about the diagnosis of TTP. B12 deficiency is common, though not typically associated with severe hematologic abnormalities. We compare the presenting characteristics of all thirteen cases of pseudo-TTP reported in the literature with those from patients in case series of TTP to suggest a set of parameters that can help clinicians distinguish between pseudo-TTP and TTP and guide decision making regarding intervention. Evaluation of all TTP cases should include a B12, methylmalonic acid level and reticulocyte count. Reticulocytopenia suggests B12 deficiency. Finally an LDH level above 2500 IU/L is relatively uncommon in TTP and should suggest consideration of B12 deficiency.