Title: Pretreatment ADAMTS13 Activity Predicts Clinical Outcome in Patients with Acquired Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2224-2224
Author(s):  
Spero R Cataland ◽  
Susan Geyer ◽  
Shangbin Yang ◽  
Haifeng Wu
Keyword(s):  
Clinical Outcome ◽  
Roc Analysis ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Significant Risk ◽  
Optimal Threshold ◽  
Suppressive Therapy ◽  
Adamts13 Activity ◽  
Increased Risk

Abstract Abstract 2224 Background: Acquired TTP is characterized by a significant risk for exacerbation (recurrent TTP within 30 days of last plasma exchange (PEX)). An algorithm applied early in the course of treatment that detects patients at increased risk for exacerbation could identify patients most likely to benefit from more intensive upfront therapy (PEX, immune-suppressive therapy) to prevent recurrence of disease after tapering PEX. We have previously reported in a small cohort study that pretreatment ADAMTS13 activity was significantly lower (0.8% v. 1.4%) in patients suffering an exacerbation, but the difference was primarily mediated by race (EJH 2009 Dec 1;83(6):559–64). We performed a study to analyze data from a large cohort of TTP patients to assess the potential prognostic utility of pretreatment ADAMTS13 activity for risk of exacerbation. Patients: Patients presenting with a clinical diagnosis of acquired TTP (platelets < 100K/uL, microangiopathic hemolytic anemia) between May 2002 and August 2010 with pretreatment ADAMTS13 activity data (86 acute TTP episodes from 49 patients evaluable for exacerbation, and 94 episodes for other factors associated with ADAMTS13 activity) were included in these analyses. Methods: Demographic and laboratory data obtained prior to starting PEX in patients with acute TTP were analyzed retrospectively to determine their relationship to early recurrences (exacerbation) of TTP. Based on these data, ROC analysis and recursive partitioning algorithms were used to determine an optimal cutoff of pretreatment ADAMTS13 activity that was prognostic for exacerbation of TTP. Subsequently, the acute TTP episodes with pretreatment ADAMTS13 <1.15% were compared to the cohort with ADAMTS13 >1.15% with respect to clinical outcomes and presenting clinical symptoms and laboratory data. Impact of these factors on exacerbation were also analyzed using generalized estimating equation models to account for multiple episodes from the same patients. Results: Overall, there were 22 exacerbation events observed in the 86 TTP episodes. There were no significant differences between subjects that suffered an exacerbation in terms of clinical laboratory data (platelet count, LDH, creatinine) at presentation. However, mean ADAMTS13 activity at presentation was significantly lower in patients that suffered exacerbations compared to those that did not [1.4% (0.5 –7.2) v. 2.9% (0.5–13.3); p=0.002]. ROC analysis of all study subjects indicated that the optimal threshold for pretreatment ADAMTS13 activity to predict the risk of exacerbation is 1.15%, which provides a test sensitivity of 64% and specificity of 62%. Subset analyses also defined the optimal threshold for AA and female populations to predict an increased risk of relapse to be 2% for both groups, giving rise to a sensitivity of 100% (AA)/82%(F) and specificity of 42% (AA)/50% (F), respectively. When using an ADAMTS13 activity threshold of 1.15% to risk stratify for increased risk for exacerbation, there were no significant differences in presenting clinical symptoms and laboratory values (Table 1). However, subjects with pretreatment ADAMTS13 activity <1.15% were more likely to suffer an exacerbation and require a greater number of PEX procedures to achieve a clinical response (platelets >150 K/uL). Conclusions: These data are among the first to suggest pretreatment ADAMTS13 activity may predict clinical outcome from an acute episode of TTP. The optimal ADAMTS13 activity threshold was 1.15%, with ADAMTS13 activity below this level being associated with an increased risk for exacerbation. Furthermore, incorporating this threshold of ADAMTS13 activity into a model with race and gender will significantly improve risk stratification and identify patients at greatest risk for early treatment failure who may be more likely to benefit from the early addition of immune-based therapy to PEX. Disclosures: No relevant conflicts of interest to declare.

Latent Myeloproliferative Neoplasm May Underlie Retinal Vein Occlusion In Older Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5242-5242
Author(s):  
Katerina Zoi ◽  
Christine Zoi ◽  
Andreas Giannopoulos ◽  
Argyri Gialeraki ◽  
Kassiani Giannaki ◽  
...  
Keyword(s):  
Retinal Vein Occlusion ◽  
Older Patients ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Significant Risk ◽  
Jak2v617f Mutation ◽  
Thrombotic Complication ◽  
Allele Burden ◽  
Vein Occlusion ◽  
Increased Risk

Abstract Background Myeloproliferative neoplasms (MPNs) have been associated with a high incidence of thrombosis and bleeding episodes, which significantly contribute to disease-related morbidity and mortality. Clinical data indicate an association of the JAK2V617F mutation, seen in nearly all polycythemia vera (PV) cases and almost 60% of those with essential thrombocythemia (ET) and myelofibrosis (MF). The mutation is also seen in 37% of patients with in splachnic vein thrombosis (SVT) and its presence was associated with an increased risk for SVT. However, the prevalence of JAK2V617 seems to be low in patients with other thromboembolic events in unusual sites such as cerebral sinus, upper limb deep venous thrombosis (DVT). Additionally, activating mutations of MPL gene, seen in 3% of ET and 5% of MF patients, are considered as a significant risk factor for microvessel disturbances and have been associated with an increased risk of arterial thrombosis. Retinal vein occlusion (RVO) is a thrombotic complication in an uncommon site that may result in sight threatening disease. In this study we investigated the prevalence of JAK2V617F and MPLW515L/K mutations in a prospectively assembled cohort of patients with RVO, hypothesizing that some cases may be associated with an underlying undiagnosed MPN. Patients and Methods We studied 52 (23 males and 29 females) consecutive patients with no evidence of an underlying MPN who had been diagnosed with RVO confirmed with fluorangiography from January 2007 to September 2011. The mean age was 70 years (range: 49-85) Twenty eight patients (53.8%) presented with central RVO and 24 patients with branched RVO (46.5%). DNA was extracted from peripheral blood samples by standard procedures. The JAK2V617F mutation was detected using a tetra-primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) assay with a sensitivity of 1% and the allele burden was estimated with a semi-quantitative method. MPLW515L/K were detected using allele-specific PCR (AS-PCR) assays with a sensitivity of 1%. Results Overall, MPN associated mutations were detected in 5/52 cases. JAK2V617F was detected in 2/52 cases (3.8%; 95%CI-1.4%-9%), while MPL exon 10 mutations were detected in 3/52 (5.7%; 95%CI-0.6%-12%). The JAK2V617F allele burden in the two positive patients was 45% and 52% respectively. Both patients who carried the JAK2V617F mutation were female. The first patient had been already diagnosed with ET according to the WHO criteria at the time of RVO screening. She was receiving hydroxyurea and aspirin and her platelet count was normal. The second patient who also carried the JAK2V617F mutation had a PLT count of 850.000/μl at the time of screening and was diagnosed with ET within the 3 following months. The patients with MPL mutations presented with normal blood counts. Conclusions Our findings indicate that a latent MPN could underlie RVO even in the absence of conventional diagnostic criteria. Our results represent the first report that MPL mutations could underlie RVO cases and suggest that routine screening of RVO cases for MPN mutations may be useful, especially in older patients. Disclosures: No relevant conflicts of interest to declare.

Exchange Transfusion and Leukapheresis in Pediatric AML Patients with High Risk of Early Death for Bleeding and Leukostasis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3741-3741
Author(s):  
Ursula Creutzig ◽  
Claudia Rossig ◽  
Michael Dworzak ◽  
Arendt von Stackelberg ◽  
Wilhelm Woessmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Exchange Transfusion ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Early Death ◽  
Myelogenous Leukemia ◽  
Acute Monocytic Leukemia ◽  
Metabolic Disturbances

Abstract Background. The risk of early death (ED) due to bleeding and/or leukostasis is high in AML patients with initial hyperleukocytosis (white blood cell count [WBC] > 100 000/µl) and highest in those with hyperleukocytosis and mono- or myelomonocytic leukemia (FAB M4/M5). (Creutzig, et al 1987) Within the AML-BFM studies, emergency strategies for children with AML and high risk for bleeding and leukostasis included exchange transfusion (ET) or leukapheresis (LPh). In order to determine whether these interventions reduced the rate of ED, 1251 AML-BFM patients from the trials AML-BFM 98 and 04 were analyzed. Risk factors for ED and interventions performed were verified focusing on patients with hyperleukocytosis. Patients . 238 of 1251 (19%) AML-patients <18 years of age (FAB M3 excluded) presented with hyperleukocytosis. Twenty-three out of 1251 (1.8%) patients died by bleeding and leukostasis within 15 days from diagnosis, 18 (78%) of these 23 ED patients had hyperleukocytosis. Seventy-two patients received ET and 17 LPh (including 14 patients with WBC counts < 100 000/µl). 149 patients with hyperleukocytosis did not receive ET/LPh. The median age of patients receiving ET was significantly lower compared to those with LPh (3.5 years vs 12.6 years, p = 0.015). WBC counts were similar in both treatment groups (ET median 224 000/µl vs LPh 218 000/µl, p = 0.20). Results. The percentage of ED by bleeding/leukostasis increased with higher WBC counts and was highest in 105 patients with WBC > 200 000/µl (14.3%). The ED rates were even higher in patients with FAB M4/M5 and hyperleukocytosis >200 000/µl compared to others with WBC >200 000/µl (M4/M5 13/65 [20%] vs. others 2/40 [5%], p=0.04). Patients with WBC counts >200 000/µl did slightly better with ET or LPh compared to those without ET/LPh (ED rate 7.5 % vs 21.2 %, p=0.055). Patients with WBC between 100 000/µl and 200 000/µl received ET/LPh less frequently compared to those with WBC >200 000/µl (22/133 [17%] vs. 53/105 [50%]). ET/LPh was mainly given in case of clinical symptoms of bleeding or leukostasis or coagulopathies or insufficient reduction (or increase) of WBC counts despite low dose chemotherapy. 15/80 (19%) patients with FAB M4/5 and WBC 100 000-200 000/µl received ET/LPh and none of these patients died early. ET/LPh was even given in 14 patients with WBC <100 000/µl because of clinical symptoms of bleeding or leukostasis or coagulopathies or rising WBC counts. In multivariate analysis WBC >200 000/µl was the strongest independent risk factor for ED (hazard ratio =15.0, 95% confidence interval 4.9-46.3, p(chi)<0.0001). FAB M4/M5 subtypes, general condition grade 4 and initial bleeding were also significant risk factors. Application of ET/LPh seems to have a non-significant benefit for a reduced ED rate by bleeding/leukostasis (p=0.13). The assessment of the general clinical condition of the patients plays a major role for the decision for ET/LPh. However, this possibly selective cofactor could not be included completely in our calculation because of lack of standardized assessments and documentation of clinical reasons for decision making in particular in patients without ET/LPh. There was no difference in ED rates between ET and LPh. (2/17 vs 5/72, p =0.61). Compared to LPh, ET can be given without time delay. ET is easier to perform especially in young children who need smaller exchange volumes, as well as in adolescents where it can be applied also as partial ET. ET also corrects metabolic disturbances and avoids deterioration of coagulation. Conclusion. Our data confirm the high risk of bleeding/leukostasis in patients with hyperleukocytosis. Although we could only disclose a trend for a clinical benefit of ET/LPh in this retrospective analysis - probably due to some negative selection bias in patients with the intervention - we strongly advocate ET/LPh in AML patients with WBC >200 000/µl, and in particular in those with FAB M4/M5 subtypes or with clinical symptoms of bleeding or leukostasis or coagulopathies even with lower WBC (100 000/µl - 200 000/µl). Creutzig, U. et al. (1987) Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia: Associations with hyperleukocytosis and acute monocytic leukemia. Cancer,60, 3071-3079. Disclosures No relevant conflicts of interest to declare.

First Infection with Absidia Corymbifera in a CLL Patient - Ibrutinib As Risk Factor?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Matthes Marquardt ◽  
Maren Thiel ◽  
Silke Kerl ◽  
Michael Wöhlke ◽  
Katrin Gröpler ◽  
...  
Keyword(s):  
Risk Factor ◽  
Clinical Outcome ◽  
Patient Group ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Left Kidney ◽  
Significant Risk ◽  
Invasive Infection ◽  
Normal Range ◽  
Absidia Corymbifera

Introduction Targeted therapy as ibrutinib, alone or in combination, is the new standard of care in CLL and has improved the clinical outcome. However, the rate of infectious side effects in the "real world" is still under debate. Several retrospective trials have observed a significant risk of invasive fungal infections (IFD) in this patient group, mostly caused by Aspergillus sp., Cryptococcus sp. or Pneumocystisjiroveci and often occurring early after initiation of the drug. Here we report the first case of an invasive infection with Absidia corymbifera, a member of the zygomyces group, in a CLL patient. The life-threatening infection occurred six years after initiation of ibrutinib treatment infiltrating and destroying the left kidney. Invasive infections with Absidia corymbifera are extremely rare and mostly reported from patients with acute leukemia or severe immunosuppression after organ transplantation. This species is not sensitive to echinoncandins and azoles with the exception of posaconazol. Thus, uncommon IFD has to be suggested in patients treated with ibrutinib treatment and invasive diagnostics should be performed early. Patient characteristics The patient, a 70 years old male, was diagnosed in 2005 with B-CLL harbouring high risk cytogenetics (deletion 17p). CLL was treated since 2005 with R-CHOP, R-bendamustine and ofatumumab before ibrutinib was started in 2014. Due to secondary antibody deficiency, the patient was substituted with IVIG every 4 weeks. At the beginning of 2020 the patient suffered three weeks from cough, fever and abdominal pain before he was admitted to our ward. We found elevated CRP (362 mg/l, normal range: &lt; 5) and procalcitonin (2.02 µg/l, normal range: &lt; 0.5), leukocytosis dominated by CLL cells, mild neutropenia (&gt; 1000 mm3) and an IgG level of 4 g/l (normal range: 7-16). A CT scan showed a barely vascularized tumor at the left kidney, peri-renal inflammation, atypical pneumonic infiltrates and multiple enlarged abdominal lymph nodes. Clinical outcome: The patient was initially treated with antibiosis and caspofungin without success. A fine-needle biopsy of the renal tumor was performed, where fungal structures were identified. Since a renal scintigraphy showed loss of function of the infected kidney, a nephrectomy was conducted to reduce the fungal load while the anti-mycotic treatment was changed to liposomal amphotericin B for three weeks. The molecular analysis of the infected kidney showed an infection with Absidia corymbifera. The patient recovered from fever and all other signs of infection under this treatment, so that he could be discharged after 4 weeks but oral posaconazole was given for additional 6 weeks. Conclusion: Here we report the first infection of a CLL patient with Absidia corymbifera, a germ only found in heavily immunosuppressed patients so far. However, ibrutinib should be considered as risk factor for uncommon invasive fungal infection. Thus, in all cases with fever of unknown origin in this patient group, lesions suspicious for IFD has to be carefully investigated and a biopsy should be taken to characterize the infectious agent. Treatment has to combine surgery and long-term antimycotic treatment. Disclosures No relevant conflicts of interest to declare.

scholarly journals 995 Clinical Outcomes Following Incomplete Colonoscopy

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
K S Khan ◽  
C McCulloch
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Incomplete Data ◽  
Significant Risk ◽  
Exclusion Criteria ◽  
Data Set ◽  
Incomplete Colonoscopy ◽  
Increased Risk ◽  
Repeat Colonoscopy

Abstract Introduction Following incomplete colonoscopy (IC) it is reported that there is up to five-fold increased risk of colorectal cancer. Our aim was to determine the final clinical outcome for patients with a prior IC. Method A multi-centre retrospective observational study involving three endoscopy units. All consecutive patients having colonoscopy from over 18 months were analysed. Exclusion criteria included IC was due to obstructing cancer, follow up was not performed due to non-attendance at clinic or investigation and incomplete data set. Electronic notes were analysed to determine patient’s final clinical outcome. All patients were followed up for minimum of six months. Results Of the 8,490 colonoscopies, 733 (8.6%) were IC. 86 (11.7%) were excluded. Of the 647 included, 469 (72.4%) were females and 473 (73.1%) has further colonic investigations. Secondary investigations were: CT colonography 169 (35.7%), repeat colonoscopy 161 (34.0%), barium enema 95 (20.1%) and others 48 (10.1%). The repeat colonoscopy group achieved a complete colonoscopy in 111 (68.9%) patients. For those who had further investigations 15 (3.2%) had colorectal cancer and 12 (2.5%) has polyps ≥1cm. Conclusions There is significant risk of missing colorectal malignancy and large polyps following IC. Further colonic investigations should be carried out in this cohort of patients.

Relationship between bacterial colonization of external cerebrospinal fluid drains and secondary meningitis: a retrospective analysis of an 8-year period

2010 ◽  
Vol 113 (6) ◽  
pp. 1309-1313 ◽  
Author(s):  
David J. Hetem ◽  
Peter A. Woerdeman ◽  
Marc J. M. Bonten ◽  
Miquel B. Ekkelenkamp
Keyword(s):  
Clinical Symptoms ◽  
Bacterial Colonization ◽  
Tertiary Care ◽  
Laboratory Data ◽  
Significant Risk ◽  
Prophylactic Antibiotic ◽  
Positive Culture ◽  
Care Hospital ◽  
Drain Removal ◽  
Microbiological Laboratory

Object A frequent complication of CSF drains is secondary meningitis. This study was designed to assess the predictive value of a positive culture from a CSF drain tip for the development of secondary meningitis. Methods The authors conducted a retrospective study of an 8-year period in which patients were treated in a tertiary care hospital in The Netherlands. Patients with positive cultures from CSF drain tips were identified from the microbiology database. Patient charts were reviewed to retrieve demographic, clinical, and laboratory data. Statistical analysis was performed using multivariate logistic regression to determine significant risk factors for the development of secondary meningitis. Results A total of 139 patients with positive CSF-drain cultures were included; 72 patients (52%) suffered secondary meningitis at the time of CSF drain removal, or developed it consecutively. Development of secondary meningitis was associated with use of ventricular drains (OR 3.4 vs lumbar drains; 95% CI 1.7–6.8), with age less than 18 years (OR 4.7; 95% CI 1.3–17.3), and with colonization with Staphylococcus aureus (OR 3.1 vs other microorganisms; CI 1.2–8.5). Thirty-two patients (44% of total secondary meningitis) were diagnosed with secondary meningitis 24 hours or more after CSF drain removal; in 13 patients (18%) the diagnosis was made after 48 hours or more. Conclusions Positive CSF-drain cultures are strongly associated with development of secondary meningitis. A positive CSF-drain culture may precede clinical symptoms and should therefore be communicated to the treating physician by the microbiological laboratory as soon as possible, and prophylactic antibiotic therapy should be considered.

Renal Disease in Sickle Cell: Clinically Varied and Associated with Increased Mortality

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 90-90
Author(s):  
Sabarish Ayyappan ◽  
Paul Drawz ◽  
Mehdi Nouraie ◽  
Mariana E Hildesheim ◽  
Yingze Zhang ◽  
...  
Keyword(s):  
Renal Function ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multivariate Analyses ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Red Cell ◽  
Cell Disease ◽  
Cell Destruction ◽  
Increased Risk

Abstract Abstract 90 The Walk-Phasst Study of sickle cell disease (SCD) affords a unique opportunity to examine renal function in a large number of adults with SCD. Extensive clinical and laboratory data were obtained on 463 adults with HbSS and 127 adults with HbSC. Where possible, correlates for estimated glomerular filtration rate (eGFR, calculated by the 4-value MDRD equation) and albuminuria/proteinuria were also evaluated in historical data, from SS adults in the CSCCD cohort and the Multicenter Study of Hydroxyurea (MSH) in sickle cell disease. Adjusted decline in eGFR was more rapid in SS compared with SC, at −2.6 and −0.92 ml/min/1.73 m2/year, respectively (p<0.001). In SS, similar declines in cross-sectional eGFR with age were seen in adults in the CSCCD (n=705) and MSH (n=298) cohorts, at −2.9 and −1.9 ml/min/year (BSA corrected), respectively. Multivariate analysis of the SS cohort in of Walk-Phasst revealed that depressed eGFR values were associated with an elevated estimated pulmonary arterial systolic pressure (as reflected in a higher tricuspid regurgitant jet velocity, measured by echocardiogram, p=0.007) and with evidence for inflammation (an elevated white blood cell count, p=0.018). In SC adults, in contrast, lower eGFRs were primarily associated with a diminished erythroid reserve (depressed absolute reticulocyte counts, P=0.005). Albuminuria (≥30 mg albumin/gm creatinine) was detectable in 66 and 41 % of adults with HbSS and HbSC in Walk-Phasst (185/287 evaluable SS and 25/61 evaluable SC, p=0.001). In Walk-Phasst, albuminuria in SS was associated with evidence of increased red cell destruction (lower total hemoglobin (P=0.07), higher LDH (P<0.001), and higher reticulocyte count (P=0.017)). In SC, albuminuria was associated with a higher LDH (P=0.01). 159/657 (24%) of adult SS subjects in the CSCCD cohort had trace to 4+ proteinuria, using a method (urine dipstick analysis) that is less sensitive and less quantitative than the albumin-to-creatinine ratio used in Walk-Phasst. Multivariate analyses again suggested a strong association between a depressed Hgb and proteinuria (P<0.001) in CSCCD, and LDH was also associated with proteinuria, in univariate analyses (P<0.001). In Walk-Phasst the absence of albuminuria in all subjects with SCD was associated with lesser mortality in multivariate analyses (Hazard ratio 0.62 (0.4–0.9, P=0.02). No similar association was seen between eGFR and mortality. Subjects with SS in Walk-Phasst had depressed serum bicarbonate levels, of 23.8±3.4 compared with 24.7±3.2mEq/dL in SC (p<0.005) and 24.8±3.3 mEq/dL in the non-CKD general population (Shah et al, 2009). In multivariate analyses, acidemia was associated with both increased destruction and decreased production of red cells, e.g. higher EPO (P=0.003) and total bilirubin levels (P<0.001), but lower reticulocyte counts (P=0.06). Impaired physiologic functioning in acidemic subjects with HbSS, manifest as a depressed 6MWD (P<0.001) and a lower eGFR (P<0.001), was seen. No effect of bicarbonate level on mortality in SCD patients was evident in Walk-Phasst. In conclusion, renal function is perturbed in sickle cell syndromes in several ways, including more rapid decrement in eGFR, highly prevalent albuminuria, and, in SS, marked abnormalities in acid-base balance. Albuminuria is associated with anemia in two large cohorts of sickle cell disease patients and, in Walk-Phasst, with evidence for enhanced red cell destruction. Importantly, albuminuria correlated with an increased risk for mortality in sickle cell disease. (We acknowledge the many contributions made by the Walk-PHASST Investigators: Badesch DB, Barst RJ, Castro OL, Girgis RE, Gibbs JS, Goldsmith JC, Hannoush H, Hassell KL, Kato GJ, Krishnamurti L, Lanzkron S, Machado RF, Morris CR, Novelli EM, Rosenzweig EB, Sachdev V, Schraufnagel DE, Taylor JG 6th.) Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Isotype of Antiphospholipid Antibodies and Their Associated Risk on Thrombosis and Pregnancy Morbidity; What Are the Odds?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1220-1220
Author(s):  
Walid Chayouâ ◽  
Hilde Kelchtermans ◽  
Gary Moore ◽  
Jean-Christophe Gris ◽  
Jacek Musial ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Solid Phase ◽  
Additional Patient ◽  
Pregnancy Morbidity ◽  
Igm Antibodies ◽  
Increased Risk

Abstract Introduction: The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL). The current aPL panel consists of detection of lupus anticoagulant (LAC), anti-cardiolipin (aCL) IgG/IgM and anti-β2glycoprotein I (aβ2GPI) IgG/IgM antibodies. Despite the fact that these aPL associate differently with the clinical symptoms of APS, all of them have the same diagnostic value in the Sydney criteria. Combined positivity has been shown to significantly increase the risk of thrombosis and pregnancy morbidity. Nonetheless, risk stratification of APS patients remains challenging. Objective: We aimed to assess the thrombotic and obstetric association of the different aPL profiles. Methods: In this multicenter study, 1068 patients from eight European medical centers were enrolled within a timespan of one year with patient samples stored less than 5 years. We included 259 thrombotic APS patients, 122 obstetric APS patients, 204 diseased controls for thrombosis (non-APS thrombosis), 33 diseased controls for obstetric complications (non-APS obstetric), 196 patients with an autoimmune disease other than APS without thrombotic complications (AID controls) and 194 patients that were referred for aPL testing for other reasons than the clinical criteria of APS (e.g. subfertility and prolonged activated partial thromboplastin time; controls). Four platforms, ACL AcuStar®, Bioplex 2200®, ImmunoCap®EliA and QUANTA Lite ELISA®, were selected based on frequency of use and the willingness of manufacturers to provide their assays. All samples with all assays were tested at one location by a single technician. Lupus anticoagulant positivity was determined by the local center, according to the ISTH guidelines. The study was approved by the local ethical committees. Results: Isolated LAC significantly correlated with thrombosis, while isolated IgG and IgM did not (Figure 1). Looking at pregnancy morbidity, significant correlations were found for both isolated LAC and isolated IgG, but not for isolated IgM (Figure 2). Based on these findings, we included both LAC and IgG testing in the first steps of risk stratification. Compared to isolated LAC positivity, with an odds ratio (OR) for thrombosis of 3.4, combined positivity for anti-β2GPI and/or anti-CL IgG antibodies increased the OR up to 5.9 (95% confidence interval [95% CI], 3.4-10.5). Positivity for LAC, IgG and IgM antibodies resulted in the highest OR for thrombosis, ranging from 5.5 (95% CI, 2.6-11.8) up to 9.6 (95% CI, 3.4-27.1), depending on the solid phase assay used (Figure 1). Other profiles including IgM showed no increased risk (insignificant OR) for thrombosis or failed to result in a higher OR compared to other profiles without IgM (Figure 1). In line with thrombosis, the highest OR for pregnancy morbidity was achieved in patients positive for LAC, IgG and IgM antibodies (Figure 2). Interestingly, a positive IgM result in the presence of a negative IgG result was not associated with pregnancy morbidity, independent of the LAC status (Figure 2). Although also other profiles were associated with pregnancy morbidity, the computed ORs were similar to isolated LAC positivity (Figure 2). Conclusions: Positivity for LAC in combination with aCL and/or aβ2GPI IgG or in combination with aCL IgM and/or aβ2GPI IgM antibodies is highly associated with thrombosis and pregnancy morbidity. Other tested aPL profiles showed equal or less correlation than isolated LAC or showed no association with thrombosis or pregnancy morbidity. Based on these findings, depending on the outcome of LAC and IgG positivity, further testing of IgM testing may not be advised as this won't provide additional information regarding risk stratification of APS patients (indicated in the red lines of the flow chart). This flowchart should be validated in additional patient cohorts and may potentially lead to an improved risk stratification of APS patients. Disclosures No relevant conflicts of interest to declare.

Risk of Thromboembolism in Patients with Paroxysmal Nocturnal Hemoglobinuria Presenting with Both Clinical Symptoms and Elevated Hemolysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1273-1273
Author(s):  
Jong-Wook Lee ◽  
Jun Ho Jang ◽  
Jin Seok Kim ◽  
Sung-Soo Yoon ◽  
Je Hwan Lee ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Chest Pain ◽  
Pharmaceutical Company ◽  
Board Of Directors ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Clinical Symptoms ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Advisory Committees ◽  
Increased Risk

Abstract Abstract 1273 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disorder characterized by chronic complement-mediated hemolysis. Chronic hemolysis is associated with an increased risk of thromboembolism (TE), the major cause of end organ damage and early mortality in PNH. Patients with PNH frequently experience clinical symptoms such as abdominal pain, chest pain, dyspnea, and hemoglobinuria. Pain and dyspnea are a likely consequence of vasoconstriction due to sequestering of nitric oxide by free hemoglobin released during hemolysis. These symptoms not only cause patient distress but may be indicative of advanced disease and an increased risk of TE. Objective: To evaluate if the risk of TE is increased in PNH patients with increased hemolysis, measured by lactate dehydrogenase (LDH) serum levels ≥1.5-fold higher than the upper limit of normal (LDH ≥1.5×ULN), plus any of the four clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria during the course of the disease, compared with patients who had an individual clinical symptom or LDH ≥1.5×ULN alone. Methods: This study included 224 PNH patients from the South Korean national PNH registry. In patients with LDH ≥1.5×ULN at diagnosis, associations between the presence of the four individual clinical symptoms and the incidence of TE were analyzed using logistic regression. The effect of multiple symptoms including LDH ≥1.5×ULN on the TE rate was assessed using odds ratios (OR) and associated 95% confidence intervals (CIs). Results: The results of the analyses between clinical symptoms, LDH ≥1.5×ULN, and the incidence of TEs are tabulated below. The risk of TE was significantly increased in patients with LDH ≥1.5×ULN (OR: 8.57; P<0.001) or who had abdominal pain, chest pain or dyspnea (OR: range 2.74–2.86; P≤0.022) during the course of the disease compared with patients without these individual symptoms. The risk of TE was further increased in patients with both LDH ≥1.5×ULN and at least one of the four symptoms compared with patients with LDH ≥1.5×ULN alone (OR: 9.20; P=0.032). Individual symptom analyses showed that patients with each symptom and LDH ≥1.5×ULN had a significantly increased risk of TE compared with patients without the symptom and LDH <1.5×ULN. This was particularly evident for abdominal pain and chest pain (OR: 17.79 and 19.04, respectively; P≤0.006) but also seen in patients with dyspnea or hemoglobinuria (OR: 10.28 and 10.35, respectively; P≤0.025). These results suggest that the combination of LDH ≥1.5×ULN and one or more of these clinical symptoms poses a much greater risk of a TE than any of the individual factors alone. Conclusions: These data confirm that hemolysis, identified by LDH ≥1.5×ULN, is a significant risk factor for TE in PNH patients. Importantly, the risk of TE was further increased in patients with both elevated hemolysis and symptoms of abdominal pain, chest pain, dyspnea or hemoglobinuria compared with patients with elevated hemolysis alone. These results suggest that early intervention is important for PNH patients with both elevated hemolysis and clinical symptoms, and also highlight the need for careful monitoring of clinical symptoms that signal an elevated clinical risk for TE. Disclosures: Lee: Alexion Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jang:Alexion Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Presentation and Outcome of Idiopathic Thrombocytopenic Purpura in Children: A Single Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4683-4683
Author(s):  
Kari Bradham ◽  
Felicia L. Wilson ◽  
Hamayun Imran
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Bone Marrow Examination ◽  
Published Data ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Increased Risk

Abstract Abstract 4683 PURPOSE: To review the presenting features, response to treatment and outcome in children diagnosed with idiopathic thrombocytopenic purpura (ITP) at the University of South Alabama, Children’s and Women’s Hospital and Specialty Clinic. METHODS: Using ICD code 287.3, data were collected from the specialty clinic’s medical records and hospital database for children diagnosed with ITP between January 2005 and September 2010. Recurrent and chronic ITP were defined as thrombocytopenia recurring within or more than 6 months of diagnosis, respectively. Univariate and multivariate logistic regression analyses were performed to evaluate variables associated with chronic ITP. RESULTS: Eight four patients were identified (M,F 1:1) with an average age of 70 months at diagnosis. Mean platelet count at presentation was 14k. Oral or nasal mucosal bleeding occurred in 19(23%) patients but none experienced a serious hemorrhage. Thirty three (39%) patients had an associated illness prior to diagnosis of ITP. Treatment consisted of intravenous immunoglobulin (IVIG) in 38(45%), WinRho in 11(13%), IVIG or WinRho followed by the other in 20(24%), data not available 8(10%) and no therapy in 7 patients (8%). Average platelet count at discharge and within 2 weeks after IVIG and WinRho was 57k, 337k and 57k, 375 respectively. Forty three (51%) were acute, 17(20%) became recurrent, and 24(29%) became chronic ITP. Bone marrow examination was performed in 26(30%) patients upon subsequent relapse but the diagnosis remained unaltered in all cases. Rituximab therapy was provided to five and splenectomy was performed in 7 patients. Four patients failed both modalities, all of whom currently are IVIG dependant. Age <5year (OR 0.12, 95%CI 0.22, 0.67, p=0.01) was protective against development of chronic ITP while platelet count >20k at presentation (OR 6.50, 95%CI 1.35, 31.30, p=0.02) and race other than white (OR 36.63, 95%CI 4.61, 291.09, p=0.001) were found to be significantly associated with the development of chronic ITP. Gender, mean platelet volume, total white cell count, and absolute lymphocyte count had no significant association. CONCLUSION: Our study supports the published data that patients with an initial platelet count >20k, older age and non-white race have an increased risk of progression to chronic ITP. Other published variables had no significant association in our analyses. Response to IVIG and WinRho was no different in our patients while rituximab or splenectomy did not lead to a complete resolution in refractory cases. Since bone marrow examination did not alter the diagnosis in any patient, we suggest that routine performance of this procedure may be omitted when a diagnosis of ITP is consistent with clinical history, physical examination and laboratory data. Disclosures: No relevant conflicts of interest to declare.

PET-CT Has Major Diagnostic Value in the Evaluation of Smoldering Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3382-3382 ◽  
Author(s):  
Brittany L. Dykstra ◽  
Shaji Kumar ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Ct Scan ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Smoldering Multiple Myeloma ◽  
Increased Risk ◽  
Pet Ct ◽  
Rate Of Progression ◽  
Risk Of Progression ◽  
Pet Ct Scan

Abstract Background: The goal of this study was to determine the predictive value of (18) F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in patients with suspected smoldering multiple myeloma (SMM), specifically to determine if a positive PET-CT was associated with a significant risk of progression to multiple myeloma (MM) within 2 years. Methods: We identified all patients with a diagnosis of SMM from January 2000 to March 2014 who had undergone a PET-CT scan as part of their clinical evaluation utilizing the Mayo Clinic Data Discovery and Query Database and a review of available medical records. The PET-CT findings, results of other diagnostic tests, and clinical course were then abstracted. A positive PET-CT was defined as radiologist interpretation of increased uptake in one or more focal areas. The primary endpoint was progression to active MM within the first 2 years following a positive PET-CT result among patients who were observed without therapy. Secondary endpoints included the proportion of patients in whom the diagnosis of active MM was made solely based on the findings of the PET-CT, the probability of progression within 2 years in patients with a negative PET-CT who were observed, and estimating differences in probability of progression based on presence or absence of underlying osteolysis in patients with a positive PET-CT. Results: 198 patients (100 male and 98 female) were identified with a suspected diagnosis of SMM in whom a PET-CT scan had been performed as part of the diagnostic evaluation. The median age was 69, range 35-92. The PET-CT was positive (defined as one or more focal lesions with increased uptake) in 82 patients, and negative in 116 patients. Of the 82 patients with a positive PET-CT, 49 were diagnosed and treated as MM, while 33 were considered to still have SMM and observed. Of the 49 patients diagnosed as MM, 12 (24%) were upstaged to the diagnosis of active disease solely based on the findings of the PET-CT; in the remaining 37 patients other MM defining events were also identified on other laboratory tests conducted during the same visit. Similarly, of the 116 patients with a negative PET-CT, 17 (15%) were diagnosed and treated as MM based on other laboratory parameters, while 99 were considered to have SMM and observed. Thus, 33 patients with a positive PET-CT and 99 patients with a negative PET-CT were observed without therapy; the rate of progression to MM within 2 years was then compared between these 2 groups. Nineteen of 33 patients (56%) with a positive PET-CT and observed as SMM progressed to active myeloma within 2 years; in contrast 27 of 99 patients (28%) with a negative PET-CT observed as SMM progressed within 2 years, P=0.0034. We then restricted the analysis to patients in whom the PET-CT was done within 90 days of diagnosis of SMM. The rate of progression within 2 years in this subset was 74% (14 of 19 patients) among those with a positive PET-CT versus 27% (12 of 44 patients) with a negative PET-CT, p=0.0015 (see Figure). Among these patients, the relative risk of progression with a positive PET-CT was 2.7 (95% CI 1.6-4.7). The median time to progression with positive PET-CT was 16 months versus 55 months with negative PET-CT, P=0.0001. Among the 19 patients with a positive PET-CT observed as SMM, the rate of progression was 77% (10 of 13 patients) among those with evidence of underlying osteolysis, and 66% (4 of 6 patients) among those without evidence of osteolysis. Conclusions: Patients with a positive PET-CT scan and underlying osteolysis when observed without therapy have a high risk (77%) of progression to MM within 2 years. This is probably an underestimate of the true risk since it excludes patients with presumably higher grade lesions on PET-CT were initiated on therapy based solely on the PET-CT finding (n=12 in this cohort). Our findings validate the recent IMWG recommendation that patients with a positive PET-CT and underlying osteolysis should be considered as active myeloma. Patients with a positive PET-CT and no underlying osteolysis are also at increased risk of progression, 66% within 2 years. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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