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Sample records for acquired thrombotic thrombocytopenic

  1. Thrombotic thrombocytopenic purpura

    MedlinePlus

    ... medlineplus.gov/ency/article/000552.htm Thrombotic thrombocytopenic purpura To use the sharing features on this page, please enable JavaScript. Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that causes blood ...

  2. Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... the NHLBI on Twitter. What Is Thrombotic Thrombocytopenic Purpura? Thrombotic thrombocytopenic purpura (TTP) is a rare blood ... kee-ay). Petechiae may look like a rash. Purpura and Petechiae The photograph shows purpura (bruises) and ...

  3. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePlus

    ... the NHLBI on Twitter. What Causes Thrombotic Thrombocytopenic Purpura? A lack of activity in the ADAMTS13 enzyme ( ... This leads to hemolytic anemia . Inherited Thrombotic Thrombocytopenic Purpura In inherited TTP, the ADAMTS13 gene is faulty. ...

  4. Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

    ClinicalTrials.gov

    2016-09-01

    Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

  5. Genetics Home Reference: thrombotic thrombocytopenic purpura

    MedlinePlus

    ... Home Health Conditions thrombotic thrombocytopenic purpura thrombotic thrombocytopenic purpura Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots ( ...

  6. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura

    PubMed Central

    Zheng, X. Long; Wu, Haifeng M.; Shang, Dezhi; Falls, Erica; Skipwith, Christopher G.; Cataland, Spero R.; Bennett, Charles L.; Kwaan, Hau C.

    2010-01-01

    Background Type G immunoglobulins against ADAMTS13 are the primary cause of acquired (idiopathic) thrombotic thrombocytopenic purpura. However, the domains of ADAMTS13 which the type G anti-ADAMT13 immunoglobulins target have not been investigated in a large cohort of patients with thrombotic thrombocytopenic purpura. Design and Methods Sixty-seven patients with acquired idiopathic thrombotic thrombocytopenic purpura were prospectively collected from three major U.S. centers. An enzyme-linked immunosorbent assay determined plasma concentrations of anti-ADAMTS13 type G immunoglobulins, whereas immunoprecipitation plus western blotting determined the binding domains of these type G immunoglobulins. Results Plasma anti-ADAMTS13 type G immunoglobulins from 67 patients all bound full-length ADAMTS13 and a variant truncated after the eighth TSP1 repeat (delCUB). Approximately 97% (65/67) of patients harbored type G immunoglobulins targeted against a variant truncated after the spacer domain (MDTCS). However, only 12% of patients’ samples reacted with a variant lacking the Cys-rich and spacer domains (MDT). In addition, approximately 37%, 31%, and 46% of patients’ type G immunoglobulins interacted with the ADAMTS13 fragment containing TSP1 2-8 repeats (T2-8), CUB domains, and TSP1 5-8 repeats plus CUB domains (T5-8CUB), respectively. The presence of type G immunoglobulins targeted against the T2-8 and/or CUB domains was inversely correlated with the patients’ platelet counts on admission. Conclusions This multicenter study further demonstrated that the multiple domains of ADAMTS13, particularly the Cys-rich and spacer domains, are frequently targeted by anti-ADAMTS13 type G immunoglobulins in patients with acquired (idiopathic) thrombotic thrombocytopenic purpura. Our data shed more light on the pathogenesis of acquired thrombotic thrombocytopenic purpura and provide further rationales for adjunctive immunotherapy. PMID:20378566

  7. Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan

    PubMed Central

    Matsumoto, Masanori; Bennett, Charles L.; Isonishi, Ayami; Qureshi, Zaina; Hori, Yuji; Hayakawa, Masaki; Yoshida, Yoko; Yagi, Hideo; Fujimura, Yoshihiro

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. PMID:22427934

  8. [Acquired thrombotic thrombocytopenic purpura after vascular prosthesis implantation for impending rupture of an abdominal aortic aneurysm].

    PubMed

    Naito, Chiaki; Ogawa, Yoshiyuki; Yanagisawa, Kunio; Ishizaki, Takuma; Mihara, Masahiro; Handa, Hiroshi; Isonishi, Ayami; Hayakawa, Masaki; Matsumoto, Masanori; Nojima, Yoshihisa

    2016-03-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/μl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors. PMID:27076251

  9. Thrombotic thrombocytopenic purpura preceding systemic lupus erythematosus.

    PubMed Central

    Simeon-Aznar, C P; Cuenca-Luque, R; Fonollosa-Pla, V; Bosch-Gil, J A

    1992-01-01

    The case of a patient admitted with thrombotic thrombocytopenic purpura nine years after developing systemic lupus erythematosus (SLE) is reported. Thrombotic thrombocytopenic purpura associated with SLE has been described on other occasions, but in most patients the diagnosis of SLE precedes that of thrombotic thrombocytopenic purpura. The unusual sequence and the chronological separation of the two diseases is emphasised. PMID:1575591

  10. Treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Fontana, S; Kremer Hovinga, J A; Lämmle, B; Mansouri Taleghani, B

    2006-05-01

    Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange (PE) therapy in the 1970s. Based on clinical studies, daily PE has become the first-choice therapy since 1991. Recent findings may explain its effectiveness, which may include, in particular, the removal of anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers and/or supply of ADAMTS13 in acquired idiopathic or congenital TTP. Based on currently available data, the favoured PE regimen is daily PE [involving replacement of 1-1.5 times the patient's plasma volume with fresh-frozen plasma (FFP)] until remission. Adverse events of treatment are mainly related to central venous catheters. The potential reduction of plasma related side-effects, such as transfusion-related acute lung injury (TRALI) or febrile transfusion reactions by use of solvent-detergent treated (S/D) plasma instead of FFP is not established by controlled clinical studies. Uncontrolled clinical observations and the hypothesis of an autoimmune process in a significant part of the patients with acquired idiopathic TTP suggest a beneficial effect of adjunctive therapy with corticosteroids. Other immunosuppressive treatments are not tested in controlled trials and should be reserved for refractory or relapsing disease. There is no convincing evidence for the use of antiplatelet agents. Supportive treatment with transfusion of red blood cells or platelets has to be evaluated on a clinical basis, but the transfusion trigger for platelets should be very restrictive. Further controlled, prospective studies should consider the different pathophysiological features of thrombotic microangiopathies, address the prognostic significance of ADAMTS13 and explore alternative exchange fluids to FFP, the role of immunosuppressive therapies and of new plasma saving approaches as recombinant ADAMTS13 and

  11. Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Deforche, Louis; Tersteeg, Claudia; Roose, Elien; Vandenbulcke, Aline; Vandeputte, Nele; Pareyn, Inge; De Cock, Elien; Rottensteiner, Hanspeter; Deckmyn, Hans; De Meyer, Simon F.; Vanhoorelbeke, Karen

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68–90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease. PMID:27479501

  12. Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura.

    PubMed

    Deforche, Louis; Tersteeg, Claudia; Roose, Elien; Vandenbulcke, Aline; Vandeputte, Nele; Pareyn, Inge; De Cock, Elien; Rottensteiner, Hanspeter; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68-90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease. PMID:27479501

  13. Thrombotic thrombocytopenic purpura in southeastern New England.

    PubMed

    Crowley, J P; Zaroulis, C G; O'Shea, P A; Clark, D D

    1983-05-01

    Eight patients with thrombotic thrombocytopenic purpura (TTP) originating within a 25-mile radius had their conditions diagnosed in a three-year period at a community teaching hospital in southeastern New England. In the preceding ten years, only one case of TTP had occurred in the same hospital. A niece-uncle relationship was present in two patients, and lymphocyte typing showed that they both shared an HLA haplotype. In the remaining patients, no social, familial, or environmental connection was established. Three patients died, all of whom were female. Six patients received exchange plasmapheresis with excellent responses in five. Autopsies in the three fatal cases showed widespread organ involvement with TTP but did not disclose evidence of any common underlying disease. This unusual occurrence should alert physicians to the possibility of localized outbreaks of TTP and the necessity of considering this diagnosis in all patients with unexplained thrombocytopenia. PMID:6383244

  14. ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Zheng, X. Long

    2015-01-01

    Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia. PMID:25587650

  15. Thrombotic Thrombocytopenic Purpura: Issues in Diagnosis and Treatment.

    PubMed

    Khatun, H; Morshed, M

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency fatal without prompt treatment. Plasma exchange (PEX), the treatment of choice for TTP, is not readily available and has major complications. We report seven cases of TTP, both acquired immune and secondary. Two patients had TTP secondary to malignancy and one secondary to SLE. Male to female ratio was 1:3 and median age at presentation 38 years. Six patients had moderate to very high level of LDH while one primary TTP had only mild elevation. Median haemoglobin and platelet at presentation were 6.3 gm/dL and 38 k/UL respectively. Median LDH value was 4595 u/L. All patients were treated with plasma exchange (PEX) except the two cases secondary to malignancy. One patient died of cardiac arrest during plasma exchange. None of the patients treated with PEX had relapsed over a median follow up of 18 months. PMID:26620016

  16. SYSTEMIC INFECTIONS MIMICKING THROMBOTIC THROMBOCYTOPENIC PURPURA

    PubMed Central

    Booth, Kristina K.; Terrell, Deirdra R.; Vesely, Sara K.; George, James N.

    2012-01-01

    The absence of specific diagnostic criteria, the urgency to begin plasma exchange treatment, and the risk for complications from plasma exchange make the initial evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP) difficult. Systemic infections may mimic the presenting clinical features of TTP. In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989–2010, 415 consecutive patients have been clinically diagnosed with their first episode of TTP; in 31 (7%) the presenting clinical features were subsequently attributed to a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete “pentad” of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure and fever. Four (16%) of 25 patients who had ADAMTS13 measurements had <10% activity; three patients had a demonstrable ADAMTS13 inhibitor. Compared to 62 patients with severe ADAMTS13 deficiency (<10%) who had no recognized alternative disorders, patients with systemic infections had more frequent fever, coma, renal failure, and the complete “pentad” of clinical features. Seventeen different infectious etiologies were documented. A systematic literature review identified 67 additional patients with a diagnosis of TTP or HUS and also a systemic infection. Among all 98 patients, infections with 41 different bacteria, viruses, and fungi were documented, suggesting that many different systemic infections may mimic the presenting clinical features of TTP. Initial plasma exchange treatment is appropriate in critically ill patients with diagnostic features of TTP, even if a systemic infection is suspected. Continuing evaluation to document a systemic infection is essential to determine the appropriateness of continued plasma exchange. PMID:21850657

  17. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  18. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura.

    PubMed

    Patriquin, Christopher J; Thomas, Mari R; Dutt, Tina; McGuckin, Siobhan; Blombery, Piers A; Cranfield, Tanya; Westwood, John P; Scully, Marie

    2016-06-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening condition caused by autoantibody-mediated inhibition of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 motif, 13). Therapeutic plasma exchange (TPE) improves survival, but disease may be refractory despite therapy. Management and treatment response of refractory TTP is variable, with rituximab and other immunosuppression often being used. Case reports have suggested a benefit of the proteasome inhibitor, bortezomib, possibly due to elimination of the autoreactive plasma cells producing anti-ADAMTS13 antibodies. We evaluated the effect of bortezomib in a series of primary refractory TTP patients unresponsive to intensive therapy. Bortezomib-treated patients were identified from consecutive cases managed at two UK referral centres. Demographic and clinical data were extracted from hospital records. ADAMTS13 activity was measured using a fluorescence resonance energy transfer VWF73 assay, and anti-ADAMTS13 IgG using enzyme-linked immunosorbent asssay. We identified six bortezomib-treated patients out of 51 consecutive cases of acute, acquired TTP. All patients received TPE, methylprednisolone and rituximab. Five of the six achieved complete remission with bortezomib, and one died of cardiac arrest due to underlying disease. No treatment-related adverse events were observed. Mean follow-up time after hospital discharge was 17 months (range: 3-33). Bortezomib appears effective in the treatment of a subgroup of cases with severe, refractory TTP. Prospective trials are required to further investigate this effect. PMID:27009919

  19. Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura.

    PubMed

    Han, Bowie; Page, Evaren E; Stewart, Lauren M; Deford, Cassandra C; Scott, James G; Schwartz, Lauren H; Perdue, Jedidiah J; Terrell, Deirdra R; Vesely, Sara K; George, James N

    2015-08-01

    After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty-two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory-II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP.

  20. Thrombotic thrombocytopenic purpura in the first trimester of pregnancy

    PubMed Central

    Sikka, Pooja; Chopra, Seema; Aggarwal, Neelam; Suri, Vanita; Chandrasekaran, Abi

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) occurs more commonly in women and so can be associated with pregnancy. The time during pregnancy with greatest risk for development of TTP is near term and during the post partum period. TTP occurring in early trimester is uncommon and is also associated with great maternal and fetal mortality. We report a successful outcome of pregnancy in a woman with TTP in early first trimester who was treated with therapeutic plasma exchange. PMID:23559773

  1. Thrombotic thrombocytopenic purpura: The role of ADAMTS13.

    PubMed

    Rogers, Heesun J; Allen, Charles; Lichtin, Alan E

    2016-08-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, life-threatening disease requiring prompt diagnosis and initiation of therapeutic plasma exchange to improve patient survival. However, diagnosis is often difficult because of atypical presentations and signs and symptoms that resemble other conditions. Measurements of ADAMTS13 activity, ADAMTS13 inhibitor, and ADAMTS13 autoantibody are useful for diagnosing TTP, guiding therapy, and predicting relapse. PMID:27505881

  2. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

    Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity. PMID:25879992

  3. Thrombotic thrombocytopenic purpura in a case of brucellosis.

    PubMed

    Akbayram, Sinan; Dogan, Murat; Peker, Erdal; Akgun, Cihangir; Oner, Ahmet Faik; Caksen, Hüseyin

    2011-06-01

    Thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombotic occlusions located in the microcirculation and a syndrome of microangiopathic hemolytic anemia, thrombocytopenia, fever, and renal and neurologic abnormalities. Thrombotic thrombocytopenic purpura is encountered in a variety of clinical situations such as viral, bacterial, and mycobacterial infections, autoimmune disorders, drug reactions, connective tissue disease, and solid tumors. In this report, we present TTP in a case of brucellosis because of rare presentation. A 7-year-old girl was admitted with the complaints of headache, fever, hematuria, malaise, jaundice, epistaxis, and purpura. Her physical examination revealed conjunctival pallor, scleral icterus, petechial-purpuric skin lesions on both legs, and confusion. Laboratory tests showed hematocrit 14%; hemoglobin 4.8 g/dL; platelet count 6000/mm(3), and reticulocytosis 6%. Peripheral blood smear revealed fragmented red blood cells and a complete absence of platelets. The clinical and laboratory findings were consistent with TTP. Serum antibrucella titration agglutination test was found to be 1/1280 positive.

  4. Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy

    PubMed Central

    Mwita, Julius Chacha; Vento, Sandro; Benti, Tadele

    2014-01-01

    Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome (TTP-HUS) is a rare pregnancy and postpartum complication that may simulate the more common obstetric complications, preeclampsia and the syndrome of haemolysis, elevated liver functions tests, low platelets (HELLP). We describe a 26 years old patient who presented with peri-partum TTP-HUSand was initially treated as a case of HELLP syndrome without any improvement. A brief review of the current TTP-HUS treatment options in pregnancy is also presented. PMID:25309655

  5. Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Bennett, Charles L.; Kim, Benjamin; Zakarija, Anaadriana; Bandarenko, Nicholas; Pandey, Dilip K.; Buffie, Charlie G.; McKoy, June M.; Tevar, Amul D.; Cursio, John F.; Yarnold, Paul R.; Kwaan, Hau C.; De Masi, Davide; Sarode, Ravindra; Raife, Thomas J.; Kiss, Joseph E.; Raisch, Dennis W.; Davidson, Charles; Sadler, J. Evan; Ortel, Thomas L.; Zheng, X. Long; Kato, Seiji; Matsumoto, Masanori; Uemura, Masahito; Fujimura, Yoshihiro

    2011-01-01

    Objectives We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. PMID:17868804

  6. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  7. Thrombotic thrombocytopenic purpura: diagnosis, pathogenesis and modern therapy.

    PubMed

    Eldor, A

    1998-06-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon multisystem disorder, sometimes associated with predisposing conditions such as pregnancy, cancer, exposure to certain drugs, bone marrow transplantation and HIV-1 infection. An abnormal interaction between the vascular endothelium and platelets which occurs in certain organs leads to thrombosis, endothelial proliferation, minimal inflammation and micro-angiopathic haemolysis. Recent studies suggest that endothelial cell perturbation and apoptosis caused by an as yet unknown plasma factor(s) may lead to the release of abnormal von Willebrand factor which facilitates the deposition of platelet microthrombi. Exchange transfusions of plasma or plasma-cryosupernatant remain the cornerstone of the treatment of TTP along with corticosteroids, platelet inhibitor drugs, vincristine and splenectomy. In most cases remissions can be attained, and cures are now common-although approximately one-half of the patients will relapse. While relapses are usually milder, they still carry a significant mortality and preventive therapies are not always effective.

  8. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

    PubMed Central

    Blum, Daniel; Blake, Geoffrey

    2015-01-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  9. Neglect-induced pseudo-thrombotic thrombocytopenic purpura due to vitamin B12 deficiency.

    PubMed

    Asano, Takeshi; Narazaki, Hidehiko; Kaizu, Kiyohiko; Matsukawa, Shouhei; Takema-Tochikubo, Yuki; Fujii, Shuichi; Saitoh, Nobuyuki; Mashiko, Kunihiko; Fujino, Osamu

    2015-10-01

    Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect. PMID:26387768

  10. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Rottenstreich, Amihai; Hochberg-Klein, Sarit; Rund, Deborah; Kalish, Yosef

    2016-05-01

    Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP. PMID:26245827

  11. Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange.

    PubMed

    Chai, Wanxing; Chaudhry, Abrar; Rabinowitz, Arthur P

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement. PMID:24782109

  12. Advances in the pathogenesis, diagnosis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

    PubMed

    Franchini, Massimo; Zaffanello, Marco; Veneri, Dino

    2006-01-01

    The thrombotic microangiopathies are microvascular occlusive disorders characterized by hemolytic anemia caused by fragmentation of erythrocytes and thrombocytopenia due to increased platelet aggregation and thrombus formation, eventually leading to disturbed microcirculation with reduced organ perfusion. Depending on whether brain or renal lesions prevail, two different entities have been described: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). However, not rarely the clinical distinctions between these two conditions remain questionable. Recent studies have contributed greatly to our current understanding of the molecular mechanisms leading to TTP and HUS. In this review, we briefly focus on the most important advances in the pathophysiology, diagnosis and treatment of these two thrombotic microangiopathies.

  13. Thrombotic thrombocytopenic purpura and focal segmental glomerulosclerosis associated with the use of ecstasy

    PubMed Central

    Kayar, Yusuf; Kayar, Nuket Bayram; Gangarapu, Venkatanarayana

    2015-01-01

    Ecstasy is a drug, which causes serious side effects and sometimes it can be lethal. These effects are due to idiosyncratic reactions as a result of various stimulations in adrenergic receptors. Here we present a case of a 36-year-old male patient who was diagnosed with thrombotic thrombocytopenic purpura associated with the use of ecstasy. Plasmapheresis along with methylprednisolone treatment restores patient condition to normal. PMID:25878432

  14. Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Rakhmanina, Natella; Wong, Edward CC; Davis, Jeremiah C; Ray, Patricio E

    2014-01-01

    HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression. PMID:25429351

  15. Successful rituximab treatment in an elderly patient with recurrent thrombotic thrombocytopenic purpura.

    PubMed

    Matsubara, Etsuko; Yamanouchi, Jun; Hato, Takaaki; Takeuchi, Kazuto; Niiya, Toshiyuki; Yasukawa, Masaki

    2016-07-01

    An 81-year-old man presenting with fever, neurological symptoms, thrombocytopenia, and hemolytic anemia was diagnosed with acquired idiopathic thrombotic thrombocytopenic purpura (TTP). His disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity was <1% and the ADAMTS13 inhibitor titer was 3.2 BU/ml. He received plasma exchange and steroid administration until remission was achieved. Seven months later, he suffered from paralysis of the right hand, hemolytic anemia, and thrombocytopenia. We confirmed TTP recurrence based on ADAMTS13 activity <1% and an ADAMTS13 inhibitor titer of 19.4 BU/ml. Four infusions of rituximab were administered in addition to plasma exchange and steroid pulse therapy. Platelet count recovery was observed within 5 days. No severe side effects related to rituximab occurred. Although rituximab has not been approved for TTP in Japan, we report the efficacy and safety of rituximab in an elderly patient with recurrent TTP. We suggest that rituximab therapy should be started as soon as possible for recurrent TTP in patients with high titers of ADAMTS13 inhibitor. PMID:27498731

  16. Presumptive thrombotic thrombocytopenic purpura following a hump-nosed viper (Hypnale hypnale) bite: a case report

    PubMed Central

    2014-01-01

    Hump-nosed viper bites are frequent in southern India and Sri Lanka. However, the published literature on this snakebite is limited and its venom composition is not well characterized. In this case, we report a patient with thrombotic thrombocytopenic purpura-like syndrome following envenoming which, to the best of our knowledge, has not been reported in the literature before. A 55-year-old woman from southern Sri Lanka presented to the local hospital 12 hours after a hump-nosed viper (Hypnale hypnale) bite. Five days later, she developed a syndrome that was characteristic of thrombotic thrombocytopenic purpura with fever, thrombocytopenia, microangiopathic hemolysis, renal impairment and neurological dysfunction in the form of confusion and coma. Her clinical syndrome and relevant laboratory parameters improved after she was treated with therapeutic plasma exchange. We compared our observations on this patient with the current literature and concluded that thrombotic thrombocytopenic purpura is a theoretically plausible yet unreported manifestation of hump-nosed viper bite up to this moment. This study also provides an important message for clinicians to look out for this complication in hump-nosed viper bites since timely treatment can be lifesaving. PMID:24987409

  17. Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome.

    PubMed

    Mouabbi, Jason Aboudi; Zein, Rami; Kafri, Zyad; Al-Katib, Ayad; Hadid, Tarik

    2016-08-01

    In patients presenting with thrombotic thrombocytopenia purpura and non-ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized. PMID:27525072

  18. Inhibitors of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura.

    PubMed

    Tsai, H M; Li, A; Rock, G

    2001-01-01

    Thrombotic thrombocytopenic purpura (TTP), characterized by platelet thrombi in the arterioles and capillaries, is associated with antibodies that inhibit the activity of von Willebrand factor (vWF)-cleaving protease. Using a modified Bethesda method, we studied the inhibitor titers in patients who participated in the trial conducted by the Canadian Apheresis Group. Among the 41 patients investigated, the inhibitor titers at presentation were 1.4 +/- 1.7 U/mL (range -0.2-6.2 U/mL). Thirty-one patients (76%) had a titer > or = 0.2 U/mL, 8 patients (20%) had a titer > or = 2.0 U/mL but none had a titer > or = 10 U/mL. Among the 33 patients with an inhibitor titer < 2.0 U/mL (low titer group) and the 8 patients with an inhibitor titer > or = 2 U/mL (high titer group), 20 (61%) and 8 (100%) respectively had a platelet count < 25x10(9)/L (P = 0.04). Neurological abnormalities were among the presenting problems in 19 (58%) of the low titer and 6 (75%) of the high titer groups. Among the 23 patients who were randomized to plasma exchange, 5 patients had an inhibitor titer > or = 2 U/mL and none responded at the end of the first treatment cycle, while 8 of the 18 patients (44%) with a titer < 2 U/mL responded. This study shows that inhibitors of vWF-cleaving protease are of low titers in most cases of acquired TTP. A higher inhibitor titer is associated with a more advanced stage of the disease and may delay the response to plasma exchange.

  19. Refractory thrombotic thrombocytopenic purpura associated with oral contraceptives and factor V Leiden: a case report

    PubMed Central

    Tsirakis, George; Mantadakis, Elpis; Xylouri, Irini; Foudoulakis, Andreas; Vardaki, Eleftheria; Katsipi, Irene; Daphnis, Eugene; Samonis, George

    2009-01-01

    Introduction Thrombotic microangiopathies constitute a heterogeneous group of diseases characterised by microangiopathic haemolytic anaemia and thrombocytopaenia associated with platelet aggregation in the microcirculation responsible for ischaemic manifestations. Classically, thrombotic microangiopathies are described as encompassing two main syndromes: thrombotic thrombocytopaenic purpura and the haemolytic-uraemic syndrome Many cases of idiopathic thrombotic thrombocytopaenic purpura have, to date, been associated with severe ADAMTS13 metalloprotease deficiency while haemolytic uraemic syndrome usually occurs in the context of normal protease activity. Oestrogens and factor V Leiden have rarely been implicated in the pathogenesis of thrombotic microangiopathy. Case presentation We describe the case of a 17-year-old female with refractory thrombotic thrombocytopaenic purpura. The patient was receiving a new generation of oral contraceptives for dysmenorrhoea and had factor V Leiden. After undergoing prolonged and intense plasma exchange therapy for 40 days and high dose oral corticosteroids therapy for 90 days, our patient recovered fully. Conclusion Patients with refractory thrombotic thrombocytopaenic purpura should likely be evaluated for congenital thrombophilic disorders and for ingestion of drugs that have been associated with this rare form of thrombotic microangiopathy. Identification of these and as yet other unknown genetic and/or acquired risk factors may lead to more judicious treatment approaches. PMID:19829833

  20. The role of splenectomy in multimodality treatment of thrombotic thrombocytopenic purpura.

    PubMed Central

    Schneider, P A; Rayner, A A; Linker, C A; Schuman, M A; Liu, E T; Hohn, D C

    1985-01-01

    Current treatment modalities for thrombotic thrombocytopenic purpura (TTP) include plasmapheresis (PP), splenectomy, steroids, dextran, other antiplatelet agents, and vinca alkaloids. Prior to the development of PP and use of multimodality treatment for TTP, mortality rates exceeded 50%. This report reviews 11 patients treated for TTP, demonstrates the successful use of splenectomy as salvage therapy, and defines our indications for splenectomy in the treatment of this disorder. Ten of 11 patients were initially treated with PP; three responded completely and one died of fulminant disease. Six patients had a transient partial response to plasmapheresis and were subsequently treated with splenectomy, steroids, and dextran-70. Initial plasmapheresis resulted in improvement in laboratory values and clinical status in those patients requiring splenectomy. Durable remission (6-48 months) was achieved in 91% of patients with minimal morbidity. PMID:2412500

  1. Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab.

    PubMed

    Khodor, Sara; Castro, Miguel; McNamara, Colin; Chaulagain, Chakra P

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases. PMID:26684918

  2. Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances in diagnosis, pathophysiology, and management.

    PubMed

    Brailey, L L; Brecher, M E; Bandarenko, N

    1999-02-01

    Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP) syndrome and improve mortality and relapse rates are hindered by its poorly understood pathophysiology. Variability in the application of therapeutic plasma exchange (TPE), including replacement fluid strategies, desirable endpoints in the platelet count, serum lactate dehydrogenase concentration, and the use of a TPE taper, limit comparisons among published studies. The diversity of adjunctive therapies such as antiplatelet agents, steroids, and splenectomy further clouds comparisons. Recent progress in the diagnosis, pathophysiology, and management of TTP syndrome are summarized. The possible role of occult infection and newly emerging associations such as ticlopidine therapy are discussed. Advances in possible pathogenic mechanisms, the rationale for different replacement fluids including the recently licensed solvent-detergent treated plasma, and progress in the apheresis management of TTP syndrome are presented.

  3. When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura

    PubMed Central

    Panchabhai, Tanmay S.; Patil, Pradnya D.; Riley, Elizabeth C.; Mitchell, Charlene K.

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12 deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12 deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12 deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12 deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12 deficiency. Vitamin B12 replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion. PMID:27308258

  4. When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura.

    PubMed

    Panchabhai, Tanmay S; Patil, Pradnya D; Riley, Elizabeth C; Mitchell, Charlene K

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12 deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12 deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12 deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12 deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12 deficiency. Vitamin B12 replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion. PMID:27308258

  5. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

    PubMed Central

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications. PMID:26609455

  6. A complement-dependent model of thrombotic thrombocytopenic purpura induced by antibodies reactive with endothelial cells.

    PubMed

    Ren, Guohui; Hack, Bradley K; Minto, Andrew W; Cunningham, Patrick N; Alexander, Jessy J; Haas, Mark; Quigg, Richard J

    2002-04-01

    Thrombotic thrombocytopenic purpura (TTP) is an immunologically mediated disease characterized by thrombocytopenia, hemolytic anemia, and pathologic changes in various organs, including the kidney, which are secondary to widespread thromboses. Central to TTP is platelet activation, which may occur from a variety of mechanisms, including endothelial cell activation or injury. In this study, injection of K6/1, a monoclonal antibody with widespread reactivity toward endothelia, led to dose-dependent thrombocytopenia in rats. This was magnified if animals were preimmunized with mouse IgG, thereby resulting in an accelerated autologous phase of injury. In this setting, significant anemia also resulted. Rats injected with K6/1 developed renal injury, consisting of tubular damage and glomerular thrombi. Thrombocytopenia and renal morphological abnormalities were eliminated if animals were complement depleted with cobra venom factor prior to K6/1 injection and worsened when the activity of the ubiquitous complement regulator Crry was inhibited with function-neutralizing antibodies. Therefore, we have developed a complement-dependent model of TTP in rats by injecting monoclonal antibodies reactive with endothelial cells. Antibody-directed complement activation leads to stimulation of platelets, through direct interactions with complement fragments and/or indirectly through endothelial cell activation or injury, with the subsequent development of TTP.

  7. Thrombotic thrombocytopenic purpura after prophylactic cefuroxime axetil administered in relation to a liposuction procedure.

    PubMed

    Eskazan, Ahmet Emre; Salihoglu, Ayse; Gulturk, Emine; Ongoren, Seniz; Soysal, Teoman

    2012-04-01

    Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is characterized by platelet and von Willebrand factor (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen vascular disease, cancer, bone marrow transplantation, and drugs (including cephalosporins). Postoperative TTP has been reported after vascular surgery, renal and liver transplantations, and orthopedic, urologic, and abdominal surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the mortality rates, but sometimes patients may have to receive immunosuppressive drugs including vincristine (VCR). This report describes a 42-year-old woman with TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction procedure who was treated successfully with plasma exchange and VCR. The patient fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP still is in remission after 6 months of follow-up evaluation. To the authors' knowledge, this is the first report in the literature describing a patient with TTP after cefuroxime axetil administered in relation to a surgical procedure who was treated successfully with TPE and VCR.

  8. Residual plasmatic activity of ADAMTS13 is correlated with phenotype severity in congenital thrombotic thrombocytopenic purpura.

    PubMed

    Lotta, Luca A; Wu, Haifeng M; Mackie, Ian J; Noris, Marina; Veyradier, Agnes; Scully, Marie A; Remuzzi, Giuseppe; Coppo, Paul; Liesner, Ri; Donadelli, Roberta; Loirat, Chantal; Gibbs, Richard A; Horne, April; Yang, Shangbin; Garagiola, Isabella; Musallam, Khaled M; Peyvandi, Flora

    2012-07-12

    The quantification of residual plasmatic ADAMTS13 activity in congenital thrombotic thrombocytopenic purpura (TTP) patients is constrained by limitations in sensitivity and reproducibility of commonly used assays at low levels of ADAMTS13 activity, blunting efforts to establish genotype-phenotype correlations. In the present study, the residual plasmatic activity of ADAMTS13 was measured centrally by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (limit of detection = 0.5%) in 29 congenital TTP patients. The results were used to study correlations among ADAMTS13 genotype, residual plasmatic activity, and clinical phenotype severity. An ADAMTS13 activity above 0.5% was measured in 26 (90%) patients and lower levels of activity were associated with earlier age at first TTP episode requiring plasma infusion, more frequent recurrences, and prescription of fresh-frozen plasma prophylaxis. Receiver operating characteristic curve analysis showed that activity levels of less than 2.74% and 1.61% were discriminative of age at first TTP episode requiring plasma infusion < 18 years, annual rate of TTP episodes > 1, and use of prophylaxis. Mutations affecting the highly conserved N-terminal domains of the protein were associated with lower residual ADAMTS13 activity and a more severe phenotype in an allelic-dose dependent manner. The results of the present study show that residual ADAMTS13 activity is associated with the severity of clinical phenotype in congenital TTP and provide insights into genotype-phenotype correlations.

  9. [Sudden death associated with myocardial damage caused by microthrombi in a patient with thrombotic thrombocytopenic purpura].

    PubMed

    Yamamoto, Kiyoko; Hattori, Yukinori; Shimada, Koki; Araki, Yoko; Adachi, Tatsuya; Tsushita, Keitaro

    2015-11-01

    We describe a 35-year-old woman with Down's syndrome who was admitted to a clinic with anorexia and vomiting. Since laboratory findings showed anemia (Hb 7.4 g/dl) and thrombocytopenia (0.5 × 10⁴/μl), she was transferred to our hospital for treatment. Further laboratory examinations revealed schistocytes, LDH elevation, and a negative Coombs' test. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange (PEX) and prednisolone administration were thus immediately initiated. Prior to these treatments, ADAMTS13 activity was less than 5% and inhibitors were detected at a level of 0.8 Bethesda U/ml. Although her platelet count had risen to 13.0 × 10⁴/μl by day 6 (post 4 sessions of PEX), it had decreased to 1.8 × 10⁴/μl on day 7. Despite ongoing PEX, thrombocytopenia persisted. On day 21, she suddenly died. Autopsy findings revealed no evidence of myocardial necrosis or coronary artery thrombosis. Extensive microthrombi were, however, detected in precapillary arterioles, capillaries, and post-capillary venules of the heart. Therefore, this patient's sudden death was clinically suspected to have been caused by cardiomyopathy, which had produced cardiogenic shock. PMID:26666721

  10. Refractory thrombotic thrombocytopenic purpura associated with primary Sjogren syndrome treated with rituximab: a case report.

    PubMed

    Toumeh, Anis; Josh, Navpreet; Narwal, Rawan; Assaly, Ragheb

    2014-01-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease that involves multiple organs and is rapidly fatal if left untreated. TTP is associated with multisystem symptoms, such as thrombocytopenia, microangiopathic hemolytic anemia, renal impairment, central nervous system involvement, and fever. TTP is idiopathic in about 37% of the cases and can be associated with autoimmune diseases in 13% of the cases. Autoimmune disease-associated TTP can be refractory to plasma exchange and requires immunosuppressive therapy. We report a case of a previously healthy 55-year-old African American female who presented with shortness of breath, hemolytic anemia, renal impairment, and thrombocytopenia. The diagnosis of TTP was made, and plasmapheresis was initiated. However, recurrence happened 48 hours after plasmapheresis was stopped. Autoimmune workup for refractory TTP revealed positive antinuclear antibodies, Anti-SSA, and Anti-SSB. Lip biopsy revealed findings consistent with Sjogren syndrome. Treatment with Rituximab was started, and significant clinical and laboratory response was achieved. The patient remained asymptomatic thereafter. A high clinical suspicion of autoimmune diseases is important as TTP tends to be refractory to plasma exchange in these cases, and immunosuppressive therapy is a key. PMID:23011161

  11. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors

    PubMed Central

    Martino, Suella; Jamme, Mathieu; Deligny, Christophe; Busson, Marc; Loiseau, Pascale; Azoulay, Elie; Galicier, Lionel; Pène, Frédéric; Provôt, François; Dossier, Antoine; Saheb, Samir; Veyradier, Agnès; Coppo, Paul

    2016-01-01

    Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population. PMID:27383202

  12. Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature

    PubMed Central

    Azarm, Taleb; Sohrabi, Ayatollah; Mohajer, Hamid; Azarm, Arezou

    2011-01-01

    Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment. PMID:22091257

  13. Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet.

    PubMed

    Rock, Gail; Anderson, David; Clark, William; Leblond, Pierre; Palmer, Douglas; Sternbach, Marion; Sutton, David; Wells, George

    2005-04-01

    A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1.1-3.95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.

  14. Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange.

    PubMed

    Narayanan, Parameswaran; Jayaraman, Aparna; Rustagi, Rashi S; Mahadevan, S; Parameswaran, Sreejith

    2012-07-01

    A nine-year-old girl presented with headache, purpura and mild left hemiparesis. Laboratory evaluation revealed thrombotic microangiopathy with ADAMTS13 deficiency, with auto-antibodies to ADAMTS13. She was treated with plasma exchange and steroids, following which she improved transiently, relapsing within 2 months. The relapse was refractory to conventional therapy and rituximab was tried. She had good response to rituximab and has been in remission for the past 12 months. Rituximab may be a promising option for children with acquired TTP refractory to plasma exchange and steroids.

  15. Novel Recombinant Glycosylphosphatidylinositol (GPI)-Anchored ADAMTS13 and Variants for Assessment of Anti-ADAMTS13 Autoantibodies in Patients with Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Li, Dengju; Xiao, Juan; Paessler, Michele; Zheng, X. Long

    2011-01-01

    Summary Immunoglobulin Gs (IgGs) against ADAMTS13 are major causes of acquired (idiopathic) thrombotic thrombocytopenic purpura (TTP). We report here a novel cell-based assay using glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 or variants expressed on cell membrane for assessment of autoantibodies in patients with TTP. We showed that IgGs from all 26 patients with acquired TTP bound to cells expressing a GPI anchored full-length ADAMTS13 (gFL) and a variant truncated after the spacer domain (gS). Also, IgGs from 25/26 (96.7%) of these TTP patients bound to cells expressing a GPI-anchored C-terminal fragment, TSP1 2-8 plus CUB (gT2C). In contrast, none of the 20 healthy blood donors showed detectable binding of their IgGs to the cells expressing gFL, gS, and gT2C. A moderate, but statistically significant correlation was observed between plasma concentrations of anti-ADAMTS13 IgG and positive cells expressing gFL (r=0.65), gS (r=0.67), and gT2C (r=0.42). These results suggest that the microtiter-plate assay and the cell-based assay may detect differential antigenic epitopes. Moreover, antigens clustered on cell membrane may enhance antibody binding affinity, thereby increasing analytical sensitivity. Finally, our assay was able to determine kinetic changes of plasma levels of anti-ADAMTS13 IgGs in TTP patients during plasma therapy. Together, our findings suggest that the novel cell-based assay may be applicable for rapid identification and mapping of anti-ADAMTS13 autoantibodies in patients with acquired TTP. PMID:21901237

  16. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome associated with high-dose interleukin-2 for the treatment of metastatic melanoma.

    PubMed

    Alexandrescu, Doru T; Maddukuri, Prasad; Wiernik, Peter H; Dutcher, Janice P

    2005-01-01

    Various drugs have been associated with the development of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Among the biologic agents, alpha-interferon therapy, used for treatment of hepatitis B and chronic myelogenous leukemia, has been associated with TTP in a few recent reports. The authors report the first case of TTP/HUS occurring in a metastatic melanoma patient receiving treatment with high-dose interleukin-2 (IL-2). A 57-year-old patient with malignant melanoma presented with seizures 3 days after completing the first week of high-dose IL-2, and the characteristic hematologic picture revealed TTP/HUS. This occurrence is unlikely to be explained by the association with malignant melanoma, which was not presenting with widespread visceral disease at the time of the occurrence, or by the use of other medications. Similar cytokine release profiles are encountered in TTP, HUS caused by Shiga toxin-1, HUS caused by E. coli O157, after IL-2 or IL-2-containing biochemotherapy, as well as in TTP caused by interferon-alpha. This cytokine profile could reflect a common cause, or just the presence of similar pathways involved. PMID:15725958

  17. A systematic review of randomized controlled trials for plasma exchange in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Brunskill, S J; Tusold, A; Benjamin, S; Stanworth, S J; Murphy, M F

    2007-02-01

    The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE). A systematic review was undertaken to summarize the randomized controlled trial (RCT) evidence, to date, on PE as treatment for TTP. Seven randomized RCTs were identified till May 2005. A statistical reduction in mortality was found in patients receiving PE compared with patients receiving plasma infusion (relative risk 0.31, 95% confidence interval 0.12-0.79). No statistical difference in mortality was found in trials comparing different replacement fluids for PE. There were few differences in the response to treatment and the resolution of the presenting signs of TTP in any trial. Lack of data prevented a full assessment of the incidence of adverse events. None of the studies included measured patients' quality of life. Further research is required to determine the benefits and side effects associated with different replacement fluids for PE. It is recommended that there should be consistency in the diagnostic criteria, measurement of clinical outcomes and length of follow up. Continued support of existing TTP patient registries and establishment of new registries would facilitate this. PMID:17266701

  18. Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes.

    PubMed

    Roy, V; Rizvi, M A; Vesely, S K; George, J N

    2001-03-01

    The diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) in patients following BMT are often uncertain and unsuccessful. To better understand the evaluation and management of these patients, we describe 17 patients treated with plasma exchange for a presumptive diagnosis of TTP following BMT during a 10 year period, 1989-1998. Because of the uncertainty of the diagnosis, these patients are described as having a 'TTP-like syndrome'. All 17 patients had received an allogeneic BMT. Comparison with the other 245 patients who had an allogeneic BMT during the same period demonstrated that patients with a TTP-like syndrome more frequently had unrelated and/or HLA-mismatched donors, and had also experienced more serious complications: grade III-IV acute GVHD and systemic bacterial, fungal, and viral infections. Three months after the diagnosis of the TTP-like syndrome, only four of 17 patients (24%) were alive; currently only one patient survives. These data emphasize: (1) the diagnosis of TTP following BMT is uncertain because of the presence of multiple BMT-associated complications. (2) The outcome of patients with TTP-like syndromes following BMT is poor. (3) Urgent intervention with plasma exchange when TTP is suspected following BMT may not always be appropriate. Alternative explanations for the signs and symptoms should be considered and treated aggressively. PMID:11319595

  19. Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008)

    PubMed Central

    Zakarija, Anaadriana; Kwaan, Hau C.; Moake, Joel L.; Bandarenko, Nicholas; Pandey, Dilip K.; McKoy, June M.; Yarnold, Paul R.; Raisch, Dennis W.; Winters, Jeffrey L.; Raife, Thomas J.; Cursio, John F.; Luu, Thanh Ha; Richey, Elizabeth A.; Fisher, Matthew J.; Ortel, Thomas L.; Tallman, Martin S.; Zheng, X. Long; Matsumoto, Masanori; Fujimura, Yoshihiro; Bennett, Charles L.

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions. PMID:19180126

  20. Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo

    PubMed Central

    SHELAT, S. G.; SMITH, P.; AI, J.; ZHENG, X. L.

    2008-01-01

    Summary Background Many patients with acquired thrombotic thrombocytopenic purpura (TTP) harbor autoantibodies that may bind and/or inhibit ADAMTS-13 proteolytic activity and accelerate its clearance in vivo. Methods To test this hypothesis, we determined ADAMTS-13 activity and antigen levels in parallel plasma samples from patients clinically diagnosed with TTP. Collagen binding, GST-VWF73 and FRETS-VWF73 assays were used to determine ADAMTS-13 activity and to detect inhibitory autoantibodies. Enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation plus Western blotting (IP/WB) were used to detect total anti-ADAMTS-13 IgG (inhibitory and non-inhibitory). Results Among 40 patients with TTP (21 idiopathic and 19 non-idiopathic), inhibitory autoantibodies were detected (by FRETS-VWF73) in 52% of idiopathic and 0% of non-idiopathic TTP patients. In contrast, non-inhibitory IgG autoantibodies were detected in 29% of idiopathic and 50% of non-idiopathic TTP patients. The concentration of inhibitory IgG autoantibody in idiopathic TTP patients was significantly higher than that of non-inhibitory IgG in either idiopathic or non-idiopathic TTP patients. Idiopathic TTP patients demonstrated significantly reduced ADAMTS-13 activity compared with non-idiopathic patients, but only slightly lower ADAMTS-13 antigen levels. Interestingly, patients with inhibitory autoantibodies exhibited significantly lower ADAMTS-13 antigen levels than those with only non-inhibitory IgG autoantibodies or no autoantibody. Serial plasma exchanges increased levels of ADAMTS-13 activity and antigen concurrently in patients with inhibitory autoantibodies. Conclusion The identification of severe ADAMTS-13 deficiency and autoantibodies or inhibitors appears to be assay-dependent; the inhibitory IgG autoantibodies, in addition to binding and inhibiting ADAMTS-13 proteolytic activity, may accelerate ADAMTS-13 clearance in vivo. PMID:16879212

  1. Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group.

    PubMed

    Rock, G; Shumak, K; Kelton, J; Blanchette, V S; Buskard, N; Nair, R; Spasoff, R

    1992-10-01

    The Canadian Apheresis Study Group recently completed a randomized clinical trial involving 102 patients with thrombotic thrombocytopenic purpura (TTP), in which treatment with plasma infusion and treatment with plasma exchange were compared. Thirty-three other patients were ineligible or refused to be randomly assigned in the trial. Of the 33 patients, 24 were assessed as ineligible because they would be unable to tolerate the fluid input that would occur if they were randomly assigned to receive plasma infusion. All 24 patients had oliguria and elevated creatinine and/or blood urea nitrogen level. These 24 patients were treated with acetylsalicyclic acid, dipyridamole, and plasma exchange according to the standardized protocol defined in the trial. Blood for tests of factors possibly involved in the pathogenesis of TTP was drawn before exchange and at intervals during and after exchange. The mean platelet count before exchange was 35.5 x 10(9) per L. In 12 of the 24 patients, the platelet count reached 150 x 10(9) per L or greater by 7 days after the initiation of plasma exchange. Three patients responded partially, in that their platelet count increased to at least twice that at presentation, but remained below 150 x 10(9) per L. One patient died during the first week. Of the eight other patients who experienced treatment failure at the 7-day assessment point, six subsequently responded, four while continuing to receive plasma exchange and two after plasma exchange had been discontinued. Of the 15 patients who either responded fully or responded partially by the end of the first cycle, all survived.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin-induced TTP.

    PubMed

    Patel, Ritu; Amber, Kyle T

    2016-10-01

    The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin-induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473-475, 2016. © 2015 Wiley Periodicals, Inc. PMID:26274019

  3. [A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

    PubMed

    Kato, Kuniyuki; Michishita, Yoshihiro; Oyama, Kenichi; Hatano, Yoshiaki; Nozawa, Tatsuru; Ishibashi, Masahisa; Konda, Ryuichiro; Sasaki, Akira

    2016-01-01

    A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis. PMID:26809542

  4. Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

    PubMed Central

    ULAS, ARIFE; SILAY, KAMILE; AKINCI, SEMA; AKINCI, MUHAMMED BULENT; SENDUR, MEHMET ALI; DEDE, DIDEM SENER; POLAT, YUNUS HALIL; YALCIN, BULENT

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy. PMID:26622823

  5. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study.

    PubMed

    Lancellotti, Stefano; Peyvandi, Flora; Pagliari, Maria Teresa; Cairo, Andrea; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, Ilaria; Mastrangelo, Stefano; Cavallo, Luigi; Oliva, Romina; De Cristofaro, Raimondo

    2016-01-01

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3%) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme's activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285-304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

  6. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

    PubMed

    Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L

    2012-11-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

  7. Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)

    PubMed Central

    Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M.; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.

    2013-01-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

  8. Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia.

    PubMed

    Podder, Sidhertha; Cervates, Jose; Dey, Bimalangshu R

    2015-01-01

    Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation. PMID:26464409

  9. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.

    PubMed

    Clark, William F; Rock, Gail; Barth, David; Arnold, Donald M; Webert, Kathyrn E; Yenson, Paul R; Kelton, John G; Li, Lihua; Foley, Steven R

    2015-07-01

    The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse. PMID:25855259

  10. Predictive Features of Severe Acquired ADAMTS13 Deficiency in Idiopathic Thrombotic Microangiopathies: The French TMA Reference Center Experience

    PubMed Central

    Coppo, Paul; Schwarzinger, Michael; Buffet, Marc; Wynckel, Alain; Clabault, Karine; Presne, Claire; Poullin, Pascale; Malot, Sandrine; Vanhille, Philippe; Azoulay, Elie; Galicier, Lionel; Lemiale, Virginie; Mira, Jean-Paul; Ridel, Christophe; Rondeau, Eric; Pourrat, Jacques; Girault, Stéphane; Bordessoule, Dominique; Saheb, Samir; Ramakers, Michel; Hamidou, Mohamed; Vernant, Jean-Paul; Guidet, Bertrand; Wolf, Martine; Veyradier, Agnès

    2010-01-01

    Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <30×109/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4–24.2, P<.001), serum creatinine level ≤200 µmol/L (OR 23.4, 95% CI 8.8–62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0–8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups. PMID:20436664

  11. Defining the genetics of thrombotic microangiopathies.

    PubMed

    Vieira-Martins, Paula; El Sissy, Carine; Bordereau, Pauline; Gruber, Aurelia; Rosain, Jeremie; Fremeaux-Bacchi, Veronique

    2016-04-01

    The spectrum of the thrombotic microangiopathies (TMA) encompasses a heterogeneous group of disorders with hereditary and acquired forms. Endothelial cell injury in the microvasculature is common to all TMAs, whatever the pathophysiological process. In this review we describe genetic mutations characteristic of certain TMAs and review their contributions to disease. Recent identification of novel pathologic mutations has been enabled by exome studies. The monogenic forms of TMA are more frequently caused by recessive alterations in von Willebrand factor cleaving protease ADAMST13, leading to congenital thrombotic thrombocytopenic purpura, or cobalamine C and DGKE genes, leading to an atypical hemolytic-uremic syndrome (aHUS)-like TMA. aHUS, whether idiopathic or linked to a known complement amplifying condition, is a TMA that primarily affects kidney function. It often results from a combination of an underlying genetic susceptibility with environmental factors activating the alternative complement pathway. Pathogenic variants in at least five complement genes coding for complement factor H (CFH) complement factor I (CFI), MCP (CD46), C3 and complement factor B (CFB) have been demonstrated to increase the risk of developing aHUS, but several more genes have been implicated. A new challenge is to separate disease-associated genetic variants from the broader background of variants or polymorphisms present in all human genomes that are rare, potentially functional, but may or may not be pathogenic.

  12. Cancer-associated thrombotic microangiopathy

    PubMed Central

    Govind Babu, K; Bhat, Gita R

    2016-01-01

    Cancer-associated thrombotic microangiopathy refers to a group of disorders characterised by microvascular thrombosis, thrombocytopenia, and ischaemic end-organ damage. Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura are the two major subtypes. It can be a manifestation of the malignancy itself or a complication of its therapy. The addition of several new drugs to the therapeutic armamentarium of cancer has brought to light several novel causative factors of this hitherto uncommon complication. This review covers the aetiology, pathogenesis, clinical manifestations, complications, and the management of cancer-associated thrombotic microangiopathy. Careful review of the patient’s medical records coupled with the correlation of clinical findings and laboratory reports can help clinch the diagnosis and institute appropriate treatment on time. PMID:27433282

  13. Cancer-associated thrombotic microangiopathy.

    PubMed

    Govind Babu, K; Bhat, Gita R

    2016-01-01

    Cancer-associated thrombotic microangiopathy refers to a group of disorders characterised by microvascular thrombosis, thrombocytopenia, and ischaemic end-organ damage. Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura are the two major subtypes. It can be a manifestation of the malignancy itself or a complication of its therapy. The addition of several new drugs to the therapeutic armamentarium of cancer has brought to light several novel causative factors of this hitherto uncommon complication. This review covers the aetiology, pathogenesis, clinical manifestations, complications, and the management of cancer-associated thrombotic microangiopathy. Careful review of the patient's medical records coupled with the correlation of clinical findings and laboratory reports can help clinch the diagnosis and institute appropriate treatment on time. PMID:27433282

  14. Thrombocytopenic syndromes in pregnancy.

    PubMed

    Yan, Matthew; Malinowski, Ann K; Shehata, Nadine

    2016-03-01

    The physiological changes in pregnancy result in platelet counts that are lower than in nonpregnant women. Consequently, thrombocytopenia is a common finding occurring in 7-12% of pregnant women. Gestational thrombocytopenia, the most common cause of low platelet counts, tends to be mild in most women and does not affect maternal, fetal or neonatal outcomes. Gestational thrombocytopenia needs to be distinguished from other less common causes of isolated thrombocytopenia, such as immune thrombocytopenia, which affects approximately 3% of thrombocytopenic pregnant women and can lead to neonatal thrombocytopenia. Hypertensive disorders of pregnancy and thrombotic microangiopathies are both associated with thrombocytopenia. They share a considerable number of similar characteristics and are associated with significant maternal and neonatal morbidity and rarely mortality. Accurate identification of the aetiology of thrombocytopenia and appropriate management are integral to optimizing the pregnancy, delivery and neonatal outcomes of this population. Clinical cases are described to illustrate the various aetiologies of thrombocytopenia in pregnancy and their treatment. PMID:27512485

  15. How Is Thrombotic Thrombocytopenic Purpura Treated?

    MedlinePlus

    ... and surgery. Treatments are done in a hospital. Plasma Therapy Plasma is the liquid part of your blood. It ... nutrients to your body. TTP is treated with plasma therapy. This includes: Fresh frozen plasma for people ...

  16. ADAMTS-13 in the Diagnosis and Management of Thrombotic Microangiopathies

    PubMed Central

    Sarig, Galit

    2014-01-01

    Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system cause microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management. PMID:25386342

  17. Acquired dysfunction due to the circulation of "exhausted" platelets.

    PubMed

    Pareti, F I; Capitanio, A; Mannucci, L; Ponticelli, C; Mannucci, P M

    1980-08-01

    An acquired platelet functional defect was found to be present in eight patients who presented with various clinical conditions--three with renal allograft rejection, three with the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, one with acute consumption coagulopathy due to an incompatible transfusion and one with systemic lupus erythematosus. They showed defective platelet aggregation and reduced levels of adenine nucleotides and serotonin with abnormal uptake and storage of the amine. The bleeding time was more prolonged than predicted from the platelet count. These abnormalities were strikingly similar to those occurring in patients with congenital storage pool deficiency. The acquired defect is thought to be related to the presence in the circulation of "exhausted" platelets following their in vivo exposure to inducers of the release reaction such as damaged endothelium, thrombin and immune complexes. The bleeding tendency of the underlying diseases might be aggravated by the impairment of platelet function. PMID:7405945

  18. [Thrombotic microangiopathies: HUS/TTP. Physiopathological aspects].

    PubMed

    Sánchez Avalos, J C

    2000-01-01

    In thrombotic thrombocytopenic purpura (TTP) and in the hemolytic uremic syndrome (HUS) fibrin-platelet thrombi occlude arterioles and capillaries. The mechanism of endothelial cell injury and the mechanism of thrombosis are the most important physiopathological events in this pathology and are largely unknown. In HUS due to the Shiga toxin, the lesion of the endothelial cells is due to penetration of the toxin into the cell via the Gb3 receptor. Endothelial cell death is a consequence of altered protein synthesis at the ribosomal level. Cytokines released during the inflammatory process, possibly enhance the endothelial damage. Genetic and immunologic predisposing factors for the development of HUS have also been postulated. In idiopathic, secondary and familial HUS/TTP the mechanism of endothelial lesion is unknown, but multiple responsible factors have been advocated such as infections, drugs, pregnancy, autoantibodies, apoptosis inducing molecules, etc. and other genetic, hormonal or immunologic predisposing factors may also be involved. Factor H deficiency has been blamed in familiar cases. The most important cause of microcirculation thrombosis is the thrombogenic capacity of endothelial cell "activation" or injury induced by multiple mechanisms. The predominant source of plasma vW factor multimers is apparent in the altered endothelial cell. The unusually large vWF multimers are more effective at binding to platelet glycoprotein Ib-IX and IIb-IIIa complexes and inducing aggregation, as also occurred with the low weight multimers formed with excessive proteolysis, as described in the acute phase of HUS/TTP. The recent report of congenital deficiency of a vWF protease in familial TTP and its functional inhibition by autoantibodies in acquired cases is characteristic of TTP. This protease inhibition has never been described in HUS and might represent pathogenetic differences between TTP and HUS, and contribute to the differential diagnosis, but further

  19. Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies

    PubMed Central

    Espinosa, G; Bucciarelli, S; Cervera, R; Lozano, M; Reverter, J; de la Red, G; Gil, V; Ingelmo, M; Font, J; Asherson, R

    2004-01-01

    Objective: To analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL). Methods: A computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002. Results: 46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients. Conclusions: The results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL. PMID:15140782

  20. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment

    PubMed Central

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA. PMID:27621680

  1. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment.

    PubMed

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA. PMID:27621680

  2. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment

    PubMed Central

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA.

  3. Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

    PubMed

    Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

    2013-01-01

    The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab.

  4. [Diagnostic and therapeutic guidelines of thrombotic microangiopathies of the Spanish Apheresis Group].

    PubMed

    Contreras, Enric; de la Rubia, Javier; Del Río-Garma, Julio; Díaz-Ricart, Maribel; García-Gala, José María; Lozano, Miguel

    2015-04-01

    Thrombotic microangiopathies (TMA) are disorders defined by the presence of a microangiopathic hemolytic anemia (with the characteristic hallmark of schistocytes in the peripheral blood smear), thrombocytopenia and organ malfunction of variable intensity. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are the most important forms of TMA and, without the adequate treatment, they are associated with high morbimortality. In recent years, significant advances in the knowledge of the pathophysiology of TMA have occurred. Those advances have allowed us to move from a syndromic diagnosis with a similar treatment to all entities to the search of etiologic diagnosis which would lead to a specific treatment, finally leading to a better outcome of the patient. This document pretends to summarize the current status of knowledge of the pathophysiology of TMA and the therapeutic options available, and to offer a diagnostic and therapeutic practical tool to the professionals caring for the patients.

  5. Wandering spleen: 'presentation in adolescent with high thrombotic risk'.

    PubMed

    Tchidjou, Hyppolite K; Castelluzzo, Maria A; Messia, Virginia; Luciani, Matteo; Monti, Lidia; Grimaldi, Chiara; Bernardi, Stefania; D'Argenio, Patrizia

    2014-07-01

    The term 'wandering spleen' refers to an abnormal hypermobility of the spleen, which may be congenital or acquired. The absence or abnormal laxity of splenic ligaments combined with an abnormally long and mobile vascular pedicle predispose to complications such as torsion of the splenic pedicle, infarction and splenic vein thrombosis. The clinical presentation of such disease is highly variable. In this case, we describe an asymptomatic case of wandering spleen in high thrombotic risk patients with cavernoma of splenic vein and infarction of the spleen. Physical examination was normal except the enlarged and no tender consistency spleen palpable at left iliac fossa. Ultrasonography revealed enlarged spleniform mass below its normal position suggesting vascular impairment and subsequently has been confirmed by colour Doppler ultrasound and computed tomography. The family history was positive for ischemic thrombotic vascular diseases and the screening for thrombotic risk has revealed hyperhomocysteinemia, thrombophilic homozygous gene mutations for factor V (H1299R) and MTHFR (C677T). For high thrombotic risk, prophylaxis postsplenectomy was suggested according to the international recommendations with subcutaneous low molecular weight heparin, associated with a preventive treatment with acetyl salicylic acid and folic acid along with B-vitamin. This case report may be helpful for clinicians involved in the care of splenectomized patients, because it has shown the importance of an appropriate pre and postoperative antithrombotic management to reduce as soon as possible the risk of thrombotic events in such patients after splenectomy. PMID:24509326

  6. Wandering spleen: 'presentation in adolescent with high thrombotic risk'.

    PubMed

    Tchidjou, Hyppolite K; Castelluzzo, Maria A; Messia, Virginia; Luciani, Matteo; Monti, Lidia; Grimaldi, Chiara; Bernardi, Stefania; D'Argenio, Patrizia

    2014-07-01

    The term 'wandering spleen' refers to an abnormal hypermobility of the spleen, which may be congenital or acquired. The absence or abnormal laxity of splenic ligaments combined with an abnormally long and mobile vascular pedicle predispose to complications such as torsion of the splenic pedicle, infarction and splenic vein thrombosis. The clinical presentation of such disease is highly variable. In this case, we describe an asymptomatic case of wandering spleen in high thrombotic risk patients with cavernoma of splenic vein and infarction of the spleen. Physical examination was normal except the enlarged and no tender consistency spleen palpable at left iliac fossa. Ultrasonography revealed enlarged spleniform mass below its normal position suggesting vascular impairment and subsequently has been confirmed by colour Doppler ultrasound and computed tomography. The family history was positive for ischemic thrombotic vascular diseases and the screening for thrombotic risk has revealed hyperhomocysteinemia, thrombophilic homozygous gene mutations for factor V (H1299R) and MTHFR (C677T). For high thrombotic risk, prophylaxis postsplenectomy was suggested according to the international recommendations with subcutaneous low molecular weight heparin, associated with a preventive treatment with acetyl salicylic acid and folic acid along with B-vitamin. This case report may be helpful for clinicians involved in the care of splenectomized patients, because it has shown the importance of an appropriate pre and postoperative antithrombotic management to reduce as soon as possible the risk of thrombotic events in such patients after splenectomy.

  7. Hodgkin's disease presenting as idiopathic thrombocytopenic purpura.

    PubMed Central

    Murphy, W. G.; Allan, N. C.; Perry, D. J.; Stockdill, G.

    1984-01-01

    A case of Hodgkin's disease presenting as idiopathic thrombocytopenic purpura in a 23-year-old male is reported. This is a rare presentation of Hodgkin's disease having been previously described in only two cases. PMID:6541338

  8. [Helicobacter pylori infection and idiopathic thrombocytopenic purpura].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-03-01

    There are increasing data on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on Helicobacter pylori infection and idiopathic thrombocytopenic purpura in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 306 out of the 524 patients investigated (54.8%) were positive for Helicobacter pylori infection and that the bacterium was eradicated in 83% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura is effective in increasing platelet count. However, since the studies so far published are few, sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer followup are needed to confirm these preliminary findings.

  9. Malignant Hypertension with Thrombotic Microangiopathy.

    PubMed

    Mitaka, Hayato; Yamada, Yuji; Hamada, Osamu; Kosaka, Shintaro; Fujiwara, Naoki; Miyakawa, Yoshitaka

    2016-01-01

    A 49-year-old man with malignant hypertension, acute kidney injury and mental deterioration was referred to our hospital. We initially observed microangiopathic hemolytic anemia, thrombocytopenia and kidney damage, indicating he had thrombotic microangiopathy (TMA). We considered TMA was caused by malignant hypertension and therefore did not start plasma therapy. The French TMA reference center reported that platelet counts and serum creatine levels have high values for predicting severe ADAMTS13 deficiency. The patient fully recovered from his illness after treatment with antihypertensive drugs and intermittent hemodialysis. This case might thus be useful to understand the proper differential diagnosis and treatment of TMA. PMID:27523008

  10. Thrombotic microangiopathy in renal allografts

    PubMed Central

    Radha, S.; Tameem, Afroz; Sridhar, G.; Aiyangar, A.; Rajaram, K. G.; Prasad, R.; Kiran, K.

    2014-01-01

    Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation. It is a morphological expression of various etiological factors. In a renal allograft, TMA can occur de novo or be a recurrent disease. The aim of this study was to analyze the etiological factors and observe the changing trends of TMA with respect to emerging new etiological factors. We evaluated 131 graft biopsies over a period of 2½ years (2010-2012). All the renal biopsies were formalin fixed, paraffin embedded. Twenty serial sections were studied. Stains routinely used were Hematoxylin and Eosin, Periodic Acid Schiff, Massons Trichrome and Silver Methenamine stains. C4d by immunohistochemical method was done on all graft biopsies. Incidence of TMA in our series was 9.1%. Out of the 12 cases, five were associated with calcineurin inhibitor toxicity, three were diagnosed as acute antibody-mediated rejection, and two were recurrent haemolytic uremic syndrome. One patient developed haemolytic uremic syndrome on treatment with sirolimus and one patient was cytomegalovirus positive on treatment with ganciclovir, developed haemolytic uremic syndrome during treatment course. This study describes a spectrum of etiological factors for thrombotic mciroangiopathy ranging from common cause like calcineurin inhibitor toxicity to rare cause like ganciclovir induced TMA. PMID:24574627

  11. Thrombotic microangiopathy in renal allografts.

    PubMed

    Radha, S; Tameem, Afroz; Sridhar, G; Aiyangar, A; Rajaram, K G; Prasad, R; Kiran, K

    2014-01-01

    Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation. It is a morphological expression of various etiological factors. In a renal allograft, TMA can occur de novo or be a recurrent disease. The aim of this study was to analyze the etiological factors and observe the changing trends of TMA with respect to emerging new etiological factors. We evaluated 131 graft biopsies over a period of 2½ years (2010-2012). All the renal biopsies were formalin fixed, paraffin embedded. Twenty serial sections were studied. Stains routinely used were Hematoxylin and Eosin, Periodic Acid Schiff, Massons Trichrome and Silver Methenamine stains. C4d by immunohistochemical method was done on all graft biopsies. Incidence of TMA in our series was 9.1%. Out of the 12 cases, five were associated with calcineurin inhibitor toxicity, three were diagnosed as acute antibody-mediated rejection, and two were recurrent haemolytic uremic syndrome. One patient developed haemolytic uremic syndrome on treatment with sirolimus and one patient was cytomegalovirus positive on treatment with ganciclovir, developed haemolytic uremic syndrome during treatment course. This study describes a spectrum of etiological factors for thrombotic mciroangiopathy ranging from common cause like calcineurin inhibitor toxicity to rare cause like ganciclovir induced TMA.

  12. Platelet microparticles in immune thrombocytopenic purpura in pediatrics.

    PubMed

    Tantawy, Azza A G; Matter, Randa M; Hamed, Ahmed A; Shams El Din El Telbany, Manal A

    2010-05-01

    Immune thrombocytopenic purpura (ITP) is one of the most common hemorrhagic disorders in childhood. Platelet microparticles (PMPs) arise with platelet activation with procoagulant activity. Elevated PMP levels in adult ITP were reported to be thrombogenic in certain settings. However, their clinical significance in pediatric ITP was not studied. The aims of this study were to assess PMP levels in ITP in children and adolescents, and its correlation with clinical status and bleeding score. The study included 40 ITP patients (20 acute aged 9 +/- 2.19 years and 20 chronic aged 10.8 +/- 4.7 years) randomly selected from the Hematology Clinic, Children's Hospital, Ain Shams University, Cairo, Egypt, and 30 sex- and age-matched healthy controls aged 9 +/- 3.28 years. Patients were subjected to detailed history, assessment of bleeding score, complete hemogram, cytological bone marrow examination, and PMP quantification in peripheral blood by flow cytometry. Acute ITP patients had significant increase in PMPs, PMP/platelet count, and PMP percent compared to controls (P = .002, P < .0001, P < .0001, respectively) and compared to chronic ITP patients (P < .0001, P < .0001, P < .0001, respectively). PMPs were significantly decreased in chronic ITP patients compared to controls (P = .001), but PMP/platelet and PMP percent showed highly significant increase in chronic ITP (P < .0001). No correlation was evident between PMP levels and platelet count in either group (P > .05). Neither higher bleeding score nor thrombotic manifestations were observed in the studied ITP patients with high PMP levels. Elevated PMP levels may be protective against severe bleeding events in pediatric ITP. The role of PMP studies in deciding the management plan of childhood and adolescent ITP needs further evaluation.

  13. Thrombotic recurrences and bleeding events in APS vascular patients: a review from the literature and a comparison with the APS Piedmont Cohort.

    PubMed

    Bazzan, M; Vaccarino, A; Stella, S; Bertero, M T; Carignola, R; Montaruli, B; Roccatello, D; Shoenfeld, Y

    2013-06-01

    In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bleeding events, therapeutic strategies, antiphospholipid (aPL) profile, inherited and acquired risk factors (when present) were calculated and compared. Emerging risk factors for thrombotic recurrences include withdrawal of oral anticoagulant therapy (OAT), high intensity OAT (INR range 3-4), aPL profile (triple positivity, Miyakis types 1 and 2a profiles) and association with inherited or acquired pro-thrombotic risk factors. Moreover, there are evidences that high risk (mainly for aPL profile) APS vascular patients have a high recurrence rate in spite of correct OAT treatment. Clinical trials in this clinical setting are needed.

  14. An improbable and unusual case of thrombotic thrombocytopenia purpura.

    PubMed

    Patel, Jaymon; Patel, Preeti; Ahmed, Zohair

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission. PMID:27609730

  15. An improbable and unusual case of thrombotic thrombocytopenia purpura

    PubMed Central

    Patel, Jaymon; Patel, Preeti; Ahmed, Zohair

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission. PMID:27609730

  16. Update on the role of the complement system in the pathogenesis of thrombotic microangiopathies.

    PubMed

    Sinkovits, György; Prohászka, Zoltán

    2014-01-01

    In thrombotic microangiopathies (TMA) pathological changes of the small vessels are present, which lead to ischaemia of the affected tissues, low platelet-count and intravascular haemolytic anaemia with fragmentocytes. Two main clinical syndromes belong to the group of TMAs: the haemolytic uraemic syndrome (HUS) with kidney failure, mainly affecting children, and the thrombotic thrombocytopenic purpura (TTP), starting primarily in adulthood. HUS can be clinically classified into two forms: typical and atypical HUS, the latter being caused by defective regulation of the complement system. However, acccording to recent studies, complement activation is also present in other TMAs. Complement activation products (C3a, C5a, MAC) are able to activate endothelial cells, which results in loss of their antiinflammatory and antithrombotic potential. Activation of the complement system can also lead to direct activation of platelets and granulocytes. The consequent endothelial damage and thrombosis forms the pathological basis of the TMAs. Exploring the exact pathogenetic role of the complement system in these diseases makes the development of new therapeutic methods possible.

  17. [Companion Diagnostics for Thrombotic Disease].

    PubMed

    Masuda, Yuya; Matsuno, Kazuhiko; Shimizu, Chikara

    2015-11-01

    In recent years, thrombotic disease, including myocardial infarction and ischemic stroke, has rapidly increased in Japan. To treat and prevent thromboembolism, warfarin has been commonly prescribed for a long period as an oral anticoagulant. However, it is difficult to define an appropriate warfarin dose because of large inter-individual variability in dose requirements and the narrow therapeutic range. Recent pharmacogenomic (PGx) studies have shown that several single nucleotide polymorphisms (SNPs) in CYP2C9 (warfarin metabolic enzyme) and VKORC1 (warfarin target enzyme) are responsible for an individual's warfarin sensitivity. In order to realize personalized warfarin treatment, algorithms to estimate the required warfarin dose based on PGx are under consideration, including the cost-effectiveness. Recently, novel oral anticoagulants (NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban) have become available as well as alternatives to warfarin treatment for the prevention of ischemic stroke in non-valvular atrial fibrillation. Although NOACs are prescribed at a fixed-dose without frequent monitoring of blood coagulability, it has been reported that there is inter-individual variability in the blood concentration of dabigatran caused by gene polymorphisms. Further studies are needed to perform more effective and safer anticoagulant therapy using NOACs. Progress in PGx studies and the realization of personalized anticoagulant therapy are expected in the future. [Review]. PMID:26995878

  18. Management of immune thrombocytopenic purpura in children: potential role of novel agents.

    PubMed

    Bredlau, Amy Lee; Semple, John W; Segel, George B

    2011-08-01

    The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10 000/μL, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy. If the disease becomes 'persistent' with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP.

  19. Thrombotic storm revisited: preliminary diagnostic criteria suggested by the thrombotic storm study group.

    PubMed

    Kitchens, Craig S; Erkan, Doruk; Brandão, Leonardo R; Hahn, Susan; James, Andra H; Kulkarni, Roshni; Pericak-Vance, Margaret; Vance, Jeffery; Ortel, Thomas L

    2011-04-01

    Physicians periodically encounter patients with an extraordinarily accelerated course of hypercoagulability who develop thromboses in multiple organ systems over days to weeks. Such patients may harbor underlying hypercoagulable clinical conditions, but their clinical course sets them apart from most patients with similar risk factors. Underlying triggers of "thrombotic storm" include pregnancy, inflammation, trauma, surgery, and infection. Aggressive anticoagulant therapy may control thrombotic storm, yet thrombotic storm may resume with even brief interruptions of anticoagulant therapy. The authors of this communication formed the Thrombotic Storm Study Group in order to identify clinical characteristics of such patients, thus constructing preliminary criteria to better define, identify, and study the course of patients deemed to have thrombotic storm. The characteristics culled from these 10 patients are: younger age (oldest was 38 years old at time of presentation); at least 2 arterial or venous (or both) thromboembolic events, typically in unusual sites with or without microangiopathy; unexplained recurrence; and frequently proceeded by a trigger. The following characteristics were not used in defining thrombotic storm: underlying malignancies; use of acute myocardial infarction as a defining arterial event in the setting of established coronary artery disease; use of cocaine; thrombotic complications expected with various intravascular devices; known paroxysmal nocturnal hemoglobinuria or myeloproliferative disorders; severe trauma; and premorbid conditions.

  20. [Pregnancy and labor in idiopathic thrombocytopenic purpura].

    PubMed

    Tampakoudis, P; Billi, H; Tantanassis, T; Kalachanis, I; Garipidou, B; Sinakos, Z; Mantalenakis, S

    1995-10-01

    Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura (ITP) were retrospectively analyses. The mean age of the women was 28.2 years. Five women underwent splenectomy during childhood. The lowest maternal platelet count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only one case. Treatment was based on administration of corticosteroids with or without human-pooled immunoglobulins. Caesarian section was performed in all cases. Six newborns were healthy and had a successful subsequent course. Two infants died, one in utero because of abruptio placentae and the other one 1 month post partum because of a cerebral haematoma. After a mean follow-up of eighteen months, thrombocytopenia is still present in two women, despite the continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy. Treatment is usually successful for the mother but the risk for the fetus remains considerably high.

  1. Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients.

    PubMed

    Berti de Marinis, Giulia; Novello, Stefano; Ferrari, Silvia; Barzon, Isabella; Cortella, Irene; Businaro, Maria Antonietta; Fabris, Fabrizio; Lombardi, Anna Maria

    2016-11-01

    Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10 %) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity <10 versus ≥10 %. ADAMTS13 activity ≥10 % patients (n = 73) showed a higher prevalence of drug- (p = 0.005) and cancer-associated (p < 0.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p < 0.001), while neurological impairment was more frequent (p = 0.001) in the <10 % ADAMTS13 activity group (n = 109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p = 0.04), focal motor deficit (p < 0.001) and cranial nerve palsy (p = 0.007) were more frequent in the <10 % activity group. In our case series, a <10 % ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions.

  2. Targeted anti-thrombotic protein micelles

    PubMed Central

    Kim, Wookhyun; Haller, Carolyn; Dai, Erbin; Wang, Xiowei; Hagemeyer, Christoph E.; Liu, David R.; Peter, Karlheinz; Chaikof, Elliot L.

    2015-01-01

    Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Herein, we report the efficient design of multifunctional protein micelles bearing targeting and therapeutic proteins by one-pot transpeptidation using an evolved sortase A. Conjugation to the corona of a single-chain antibody (scFv), which binds to the ligand induced binding site (LIBS) of activated GPIIb/IIIa receptors enabled efficient detection of thrombi. Inhibiting thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for local generation of activated protein C, which serves to inhibit thrombin formation. An effective strategy has been developed for preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events. PMID:25504546

  3. Acquired bleeding disorders in the elderly.

    PubMed

    Kruse-Jarres, Rebecca

    2015-01-01

    The hemostatic balance changes with advancing age which may be due to factors such as platelet activation, increase of certain clotting factor proteins, slowing of the fibrinolytic system, and modification of the endothelium and blood flow. Generally, this predisposes the elderly to thrombosis rather than bleeding. It often necessitates antiplatelet or anticoagulation therapy, which can cause significant bleeding problems in an aging population. Additionally, changing renal function, modification in immune regulation, and a multitude of other disease processes, can give rise to acquired bleeding disorders. Bleeding can prove difficult to treat in a dynamic environment and in a population that may have underlying thrombotic risk factors.This article discusses some specific challenges of acquired bleeding arising in the elderly. The use of anticoagulation and nonsteroidal anti-inflammatory medications is prevalent in the treatment of the elderly and predisposes them to increased bleeding risk as their physiology changes. When prescribing and monitoring these therapies, it is exceedingly important to weigh thrombotic versus bleeding risks. There are additional rare acquired bleeding disorders that predominantly affect the elderly. One of them is acquired hemophilia, which is an autoimmune disorder arising from antibodies against factor VIII. The treatment challenge rests in the use of hemostatic agents in a population that is already at increased risk for thrombotic complications. Another rare disorder of intensifying interest, acquired von Willebrand syndrome, has a multitude of etiologic mechanisms. Understanding the underlying pathophysiology is essential in making a treatment decision for this disorder.

  4. [Thrombotic complications in the nephrotic syndrome].

    PubMed

    Keusch, G

    1989-08-01

    Thromboembolic episodes are one of the most serious complications in patients with nephrotic syndrome, with an overall incidence of 25%. The most frequent site of thrombosis is the renal vein, with a reported incidence varying from 2-42%. Arterial thromboses are much less common than venous thromboses, with an overall incidence of 3%. Clinical course of renal vein thrombosis may be acute or chronic. Renal venography is the method of choice in its diagnosis. Duplex scanning, computed tomography and magnetic resonance imaging may be as accurate as venography. Once the diagnosis of renal vein thrombosis is established, anticoagulation therapy should be started. Thrombectomy or thrombolytic therapy seem to have little to offer over oral anticoagulation. The increased incidence of thrombotic complications in nephrotic syndrome may be due to a hypercoagulable state distinguished by an increase in coagulation factors (V, VIII, X and fibrinogen); a decrease in the levels of coagulation inhibitors (antithrombin III, protein S); an increase in alpha 2-antiplasmin activity; and exaggerated platelet adhesiveness and aggregation. This pre-thrombotic state may be aggravated by additional rheological factors (immobilization, diuretic therapy etc.). Serum albumin has been found to be an appropriate parameter to assess the risk of thrombosis development in these patients. A serum albumin level below 20 g/l carries a high risk of thromboembolic complications. Prophylactic anticoagulation therapy is therefore indicated in patients with serum albumin below 20 g/l.

  5. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient. PMID:26242500

  6. Coexisting Situs Inversus Totalis and Immune Thrombocytopenic Purpura

    PubMed Central

    Gundogdu, Kemal; Altintoprak, Fatih; Uzunoğlu, Mustafa Yener; Dikicier, Enis; Zengin, İsmail; Yağmurkaya, Orhan

    2016-01-01

    Situs inversus totalis is a rare congenital abnormality with mirror symmetry of mediastinal and abdominal organs. Immune thrombocytopenic purpura is an autoimmune disease with destruction of thrombocytes. This paper is presentation of surgical approach to a case with coexistence of these two conditions. PMID:26981307

  7. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient.

  8. Intravenous Rh immune globulin for treating immune thrombocytopenic purpura.

    PubMed

    Sandler, S G

    2001-11-01

    Intravenous Rh [corrected] immune globulin was licensed by the U. S. Food and Drug administration in 1995 for the treatment of acute and chronic immune thrombocytopenic purpura in children and chronic immune thrombocytopenic purpura in adults. In 1996, the American Society of Hematology published a practice guideline for immune thrombocytopenic purpura, but treatment recommendations of necessity were formulated using only results of early clinical trials with intravenous Rh immune globulin. To date, there are no published results of large-scale clinical trials comparing conventional doses of intravenous immune globulin with the most promising dose range for intravenous Rh immune globulin (50-75 microg/kg). However, clinical experience is accumulating to indicate that intravenous Rh immune globulin is as effective, probably safer, and easier to administer than intravenous immune globulin. Acute intravascular hemolysis after infusions of intravenous Rh immune globulin for immune thrombocytopenic purpura has been reported with an estimated incidence of 1 in 1,115 patients. The risk factors for this adverse event have not been defined.

  9. [Laparoscopic splenectomy in immune thrombocytopenic purpura in pregnant women].

    PubMed

    Danishyan, K I; Soboleva, O A; Galstyan, G M; Zvereva, A V; Sorkina, O M

    2016-01-01

    The paper describes 4 cases of laparoscopic splenectomy in pregnant women with immune thrombocytopenic purpura. No complications of surgery were noted in all the patients. The postoperative period was marked by sustained clinical and hematological remission that made it possible to discontinue prednisolone therapy and to ensure an uncomplicated course of pregnancy and labor. PMID:27459624

  10. Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS).

    PubMed

    Bidot, Carlos J; Jy, Wenche; Horstman, Lawrence L; Ahn, Eugene R; Yaniz, Miriam; Ahn, Yeon S

    2006-06-01

    Antiphospholipid antibodies (APLA) are associated with anti-phospholipid syndrome (APS), a thrombotic disorder, but they are also frequently detected in immune thrombocytopenic purpura (ITP), a bleeding disorder. To investigate possible differences of APLA between these two disorders, we assayed IgG and IgM APLA by ELISA in 21 patients with ITP and 33 with APS. The APLA reacting against two protein target antigens, beta(2)-glycoprotein 1 (beta2GP1) and FVII/VIIa, and four phospholipids [cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE)] as well as lupus anticoagulant (LA) were analyzed. We made the following observations: (i) IgG and IgM antibodies to beta2GP1 and IgM antibodies to FVII/VIIa were more common in APS than ITP, P < 0.05, while IgG antibodies against the phospholipids (aCL, aPC, aPS, aPE) were more common in ITP than APS, P < 0.05; (ii) multiple APLA > or =3 antigens) were more frequent in APS than ITP, P < 0.05; (iii) LA was frequently associated with APS but was absent in ITP; (iv) APLA is quite common in ITP: two-thirds were positive for at least one APLA. In summary, APLA are prevalent in ITP but their profile differs from APS. In APS, antibodies were predominantly against beta2GP1 and 80% had positive LA, while in ITP the APLA reacted most often with the phospholipids without LA. The difference in APLA may result in opposite clinical manifestations in two disorders.

  11. Perioperative thrombotic complications in liver transplantation

    PubMed Central

    Feltracco, Paolo; Barbieri, Stefania; Cillo, Umberto; Zanus, Giacomo; Senzolo, Marco; Ori, Carlo

    2015-01-01

    Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation (OLT), the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival. Thromboembolism during OLT is characterized not only by a complex aetiology, but also by unpredictable onset and evolution of the disease. The initiation of a procoagulant process may be triggered by various factors, such as inflammation, venous stasis, ischemia-reperfusion injury, vascular clamping, anatomical and technical abnormalities, genetic factors, deficiency of profibrinolytic activity, and platelet activation. The involvement of the arterial system, intracardiac thrombosis, pulmonary emboli, portal vein thrombosis, and deep vein thrombosis, are among the most serious thrombotic events in the perioperative period. The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis, particularly when these events occur intraoperatively or early after OLT. Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting, many institutions recommend such an approach especially in the subset of patients at high risk. However, the decision of when, how and in what doses to use the various chemical anticoagulants is still a difficult task, since there is no common consensus, even for high-risk cases. The risk of postoperative thromboembolism causing severe hemodynamic events, or even loss of graft function, must be weighed and compared with the risk of an important bleeding. In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurring in the perioperative period, as well as their incidence and clinical features. Moreover, the indications to pharmacological prophylaxis and the current

  12. The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry.

    PubMed

    Hassan, Sevda; Westwood, John-Paul; Ellis, Debra; Laing, Chris; Mc Guckin, Siobhan; Benjamin, Sylvia; Scully, Marie

    2015-12-01

    Thrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24·57%) and haemolytic uraemic syndrome (HUS) (27·17% aHUS, 2·83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 × 10(9) /l; range 0-96) than aHUS (57 × 10(9) /l; range 13-145, P < 0·0001) or STEC-HUS (35 × 10(9) /l; range 14-106, P < 0·0001); they also had lower creatinine levels (92 μmol/l; range 43-374) than aHUS (255 μmol/l; range 23-941, P < 0·0001) and STEC-HUS (324 μmol/l; range 117-639, P < 0·0001). However, 12/34 (35·3%) aHUS patients had a platelet count <30 × 10(9) /l and 26/150 (17·3%) of TTP patients had a platelet count >30 × 10(9) /l; 23/150 (15·3%) of TTP patients had a creatinine level >150 μmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis. PMID:26359646

  13. Thrombotic Microangiopathy in the Setting of HIV Infection: A Case Report and Review of the Differential Diagnosis and Therapy.

    PubMed

    Saab, Karim R; Elhadad, Sonia; Copertino, Dennis; Laurence, Jeffrey

    2016-08-01

    Before the modern era of HIV/AIDS therapeutics, which enabled a cascade of early recognition of infection, prompt initiation of effective antiretroviral therapies, and close follow-up, severe forms of microvascular clotting disorders known as thrombotic microangiopathies (TMAs) were frequent in the setting of advanced HIV disease. Their incidence was as high as 7% in the period 1984-1999, but fell dramatically, to <0.5%, by 2002. This profound change was predicated on one critical development: availability of new classes of anti-HIV drugs, enabling reduction and maintenance of HIV viral loads to undetectable levels. Another development in the period 1999-2002 related to TMA therapy: with recognition of autoantibodies against the von Willebrand factor cleaving protease ADAMTS13 as the etiology of most cases of one major form of TMA, thrombotic thrombocytopenic purpura, it permitted appropriate use of life-saving interventions based on plasma exchange and immune suppression. A more recent factor in TMA therapeutics was the 2011 approval by the US FDA and European EMA of eculizumab, a humanized monoclonal antibody against complement component C5, for the treatment of atypical hemolytic uremic syndrome, another major form of TMA. Despite these milestones, life- and organ-threatening TMAs still occur in untreated HIV disease and, to a much lesser extent, in those patients with suppressed viral loads. Confusion in terms of the differential diagnosis of these TMAs also impedes use of directed treatments. This report utilizes a case study of a young woman with advanced AIDS who presented with a severe TMA, characterized by coma and renal failure, to highlight the diagnostic and therapeutic challenges raised by complex hematologic conditions occurring in the setting of HIV. PMID:27509235

  14. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.

    PubMed

    Bendapudi, Pavan K; Li, Ang; Hamdan, Ayad; Uhl, Lynne; Kaufman, Richard; Stowell, Christopher; Dzik, Walter; Makar, Robert S

    2015-12-01

    The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93·0% vs. 47·5%, P < 0·0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13·2-63·8%, P < 0·0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0·98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.

  15. Malignant hypertension-associated thrombotic microangiopathy following cocaine use.

    PubMed

    Lamia, Rais; El Ati, Zohra; Ben Fatma, Lilia; Zouaghi, Karim; Smaoui, Wided; Rania, Khedher; Krid, Madiha; Ben Hmida, Fathi; Béji, Soumaya; Ben Moussa, Fatma

    2016-01-01

    Cocaine is one of the most commonly used illicit drugs with distribution and consumption throughout the world. Acute renal failure associated with rhabdomyolysis, direct vasoconstriction and hemodynamic alteration is well described in patients with cocaine intoxication. Cocaine use is associated with high blood pressure and may rarely induce malignant hypertension associated with thrombotic microangiopathy. We report the case of a patient who developed malignant hypertension associated with thrombotic microangiopathy after chronic consumption of cocaine. A kidney biopsy revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. He required dialysis sessions. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop malignant hypertension associated with thrombotic microangiopathy. Clinicians need to be aware of this rare feature of cocaine intoxication. PMID:26787585

  16. Endoscopy in neutropenic and/or thrombocytopenic patients

    PubMed Central

    Tong, Michelle C; Tadros, Micheal; Vaziri, Haleh

    2015-01-01

    AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm3 in four studies and less than 10000/mm3 in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm3 in one study and less than 20000/mm3 in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm3 in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be

  17. Thrombotic microangiopathy in sickle cell disease crisis.

    PubMed

    Shome, Durjoy K; Ramadorai, Prabha; Al-Ajmi, Abdulla; Ali, Fakhriya; Malik, Neelam

    2013-04-01

    Thrombotic microangiopathy (TMA) in patients with sickle cell disease (SCD) is a rare complication. These patients manifest microangiopathic hemolytic anemia (MAHA) with laboratory evidence of hemolytic anemia, schistocytosis, and thrombocytopenia. This is the first report of the syndrome in a group of these patients. A retrospective chart analysis of 10 consecutively diagnosed patients in SCD crisis who were referred for therapeutic plasma exchange (TPE) after developing MAHA was done. Patients had chest pain, respiratory distress, fever, pulmonary infiltrates, jaundice, and neurological dysfunction with abnormal liver function and coagulation tests. MAHA was diagnosed after a median hospital stay of 5 days. Nine patients recovered completely following TPE with fluid replacement by fresh frozen plasma with or without cryo-poor plasma. Incomplete response to TPE in one case was due to the development of fresh complications. During a median follow-up period of 77 months, there was one recurrent episode and one death in SCD crisis but without evidence of MAHA. TMA is not a very rare complication among Bahraini SCD patients in crisis. Characteristic features of this disorder are acute chest syndrome, organ failure, leuco-erythroblastosis, and a combination of thrombocytopenia, LDH level >1,000 U/l, and schistocytes in blood smears. Management with TPE usually leads to complete recovery with little chance of short-term recurrence. Multiple pathogenetic mechanisms leading to increased von Willebrand factor and its multimers may form the basis of this syndrome.

  18. Immune thrombocytopenic purpura-related hemotympanum presenting with hearing loss.

    PubMed

    Fisgin, Tunc; Atmaca, Sinan; Duru, Feride; Ozyurek, Emel; Cetin, Recep; Albayrak, Davut

    2009-06-01

    A 5-year-old boy was admitted to our center with a major complaint of bilateral hearing loss for 2 days. He was diagnosed with acute immune thrombocytopenic purpura 3 months before the admission and treated with high-dose methylprednisolone 2 months ago. Physical examination revealed wet purpura in the oral mucosa, serous nasal discharge, multiple petechiae and ecchymosis of the lower lip. Otomicroscopic ear examination revealed the presence of bilateral hemotympanum. The patient denied head trauma, ear pain, fever, hypertension and medications, including salicylates. The patient received high-dose intravenous methylprednisolone because of low platelet count and wet purpura for 7 days and oral prophylactic amoxicillin-clavulanate for 14 days. The onset of the response to corticosteroids was rapid, and significant hematologic improvement was observed within a few days. The 2-week follow-up examination revealed intact tympanic membranes with normal color and mobility, and the patient restored normal hearing. In this patient, hemotympanum developed rapidly, and no predisposing cause other than immune thrombocytopenic purpura was found. However, presence of a serous nasal discharge may be a sign of viral upper respiratory tract infection. Therefore, it can be speculated that sneezing or coughing might have caused bilateral hemotympanum by increasing the middle ear pressure abruptly. We would like to emphasize that bleeding may occur in unusual sites and, unlike in healthy people, may cause bizarre symptoms in patients with bleeding diathesis. Hemotympanum can be considered among the indications to start treatment in patients with acute immune thrombocytopenic purpura. PMID:19530341

  19. Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

    PubMed Central

    Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, Işıl

    2014-01-01

    Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/μL. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

  20. [Pre-Thrombotic (Hypercoagulable) State/Hypercoagulable Disease].

    PubMed

    Wada, Hideo

    2015-12-01

    A pre-thrombotic (hypercoagulable) state is observed in patients with thrombophilia, malignant diseases, pregnancy, auricular fibrillation, connective tissue diseases, prosthetic replacement arthroplasty, infection, or old age, and these states are also caused by dehydration, remaining in the same position for a long time, or estrogen drugs. Such patients have a high risk of developing thrombosis. The pre-thrombotic state is diagnosed or excluded by fibrin-related markers (FRMs), such as soluble fibrin (SF), fibrinogen and fibrin degradation products (FDP), and D-dimer. The cut-off values of FRMs are higher in patients with pregnancy or malignant diseases than in other patients. Patients with more than two of the eight underlying states and three causative factors for pre-thrombotic conditions or those with one of those conditions and high levels of FRMs are diagnosed as being in a prethrombotic state. These patients should receive treatment with anticoagulant therapy. PMID:27089657

  1. Helicobacter pylori-associated idiopathic thrombocytopenic purpura: a narrative review.

    PubMed

    Franchini, Massimo; Vescovi, Pier Paolo; Garofano, Massimo; Veneri, Dino

    2012-07-01

    The Gram-negative bacterium Helicobacter pylori has a well-demonstrated role in several gastroduodenal diseases, including peptic ulcer disease, chronic active gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In addition, more recently, several studies have focused on the possible causal role of H. pylori in various extragastric disorders, such as cardiovascular, respiratory, neurological, skin, and autoimmune conditions. The current status of the research on the pathogenesis, clinical and therapeutic aspects of H. pylori-associated idiopathic thrombocytopenic purpura in adults and children will be addressed in this narrative review.

  2. Accessory spleen compromising response to splenectomy for idiopathic thrombocytopenic purpura

    SciTech Connect

    Ambriz, P.; Munoz, R.; Quintanar, E.; Sigler, L.; Aviles, A.; Pizzuto, J.

    1985-06-01

    Accessory spleens were sought in 28 patients who had undergone splenectomy for chronic idiopathic thrombocytopenic purpura (ITP), using a variety of techniques. Abdominal scintigraphy with autologous erythrocytes labeled with Tc-99m and opsonized with anit-D IgG (radioimmune method) proved to be most useful, clearly demonstrating one or more accessory spleens in 12 cases (43%). Computed tomography (CT) was also helpful. Four out of five patients demonstrated an increased platelet count following surgery, the effectiveness of which was illustrated by the radioimmune scan. Patients who have had splenectomy for chronic ITP should be scanned using radioimmune techniques and CT to determine whether an accessory spleen is present.

  3. Thrombotic Microangiopathy Revealing Bone Metastases from an Ethmoid Sinus Carcinoma

    PubMed Central

    Morisse, Mony Chenda; Kontar, Loay; Bihan, Céline; Boone, Mathieu; Lachaier, Emma; Titeca-Beauport, Dimitri; Maizel, Julien; Chauffert, Bruno

    2016-01-01

    Cancer-related thrombotic microangiopathy (TMA) is a rare entity whose clinical and biological characteristics have been described in various tumors. Here we describe the first case of cancer-related TMA revealing diffuse bone metastases from an ethmoid sinus carcinoma. PMID:27721770

  4. Nonbacterial thrombotic endocarditis: A rare manifestation of gynecologic cancer.

    PubMed

    Orfanelli, Theofano; Sultanik, Elliot; Shell, Roger; Gibbon, Darlene

    2016-08-01

    •Nonbacterial thrombotic endocarditis (NBTE) is a rare complication of cancer.•NBTE may precede the diagnosis of an occult gynecologic malignancy.•Malignancy-induced NBTE must be considered in patients with unprovoked venous thromboembolism.•The most effective treatment is anticoagulation and treatment of the underlying cancer.

  5. Nonbacterial thrombotic endocarditis: A rare manifestation of gynecologic cancer.

    PubMed

    Orfanelli, Theofano; Sultanik, Elliot; Shell, Roger; Gibbon, Darlene

    2016-08-01

    •Nonbacterial thrombotic endocarditis (NBTE) is a rare complication of cancer.•NBTE may precede the diagnosis of an occult gynecologic malignancy.•Malignancy-induced NBTE must be considered in patients with unprovoked venous thromboembolism.•The most effective treatment is anticoagulation and treatment of the underlying cancer. PMID:27453927

  6. [Long-term follow-up of chronic idiopathic thrombocytopenic purpura in children].

    PubMed

    Amendola, G; Danise, P; D'Arco, A

    2000-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a common acquired bleeding disorder in infancy and childhood. Most children rapidly improve, exhibiting a rise in platelet count to hemostatically normal levels within weeks to several months. Traditionally, chronic ITP is defined as persistence of thrombocytopenia (platelet count < 150 x 10(9)/L) for greater than 6 months. The Authors retrospectively evaluated 16 patients with chronic ITP, identified during a 12-year period of time in their Department of Pediatrics. The most important clinical and hematological parameters of patients were analyzed, including age at diagnosis, type and response to the initial treatment, number of multiple treatments, and duration of follow-up. At the last evaluation (december 1999) one patient was lost to the follow-up; one died of overwhelming postsplenectomy sepsis; four still require intermittent or chronic infusions of intravenous gamma-globulin; seven are in stable partial remission (PLT > 50 x 10(9)/L < 150 x 10(9)/L) and do not require any treatment; three are in complete remission (PLT > 150 x 10(9)/L). Finally, the Authors discuss of the natural history and management of this rare disease. Presently there are insufficient trial data to support evidence-based treatment guidelines in childhood chronic ITP and therefore it is reasonable to encourage future multicentre collaboration.

  7. Acquired lymphangiectasis.

    PubMed

    Celis, A V; Gaughf, C N; Sangueza, O P; Gourdin, F W

    1999-01-01

    Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as a complication of surgical intervention and radiation therapy for malignancy. Acquired lymphangiectasis shares clinical and histologic features with the congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these vesiculo-bullous lesions is important because they may be associated with pain, chronic drainage, and cellulitis. We describe two patients who had these lesions after treatment for cancer and review the pertinent literature. Although a number of treatment options are available, we have found CO2 laser ablation particularly effective. PMID:9932832

  8. Retinal artery and vein thrombotic occlusion during pregnancy: markers for familial thrombophilia and adverse pregnancy outcomes

    PubMed Central

    Kurtz, Will S; Glueck, Charles J; Hutchins, Robert K; Sisk, Robert A; Wang, Ping

    2016-01-01

    Background Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. Specific aim We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. Results Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40–60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal–placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. Conclusion OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent

  9. [Progress of laboratory diagnosis of hemorrhagic and thrombotic diseases--specialized to cross-mixing test--introduction].

    PubMed

    Komiyama, Yutaka

    2009-10-01

    Laboratory diagnosis of hemorrhagic and thrombotic diseases, especially cross-mixing tests, was developed because the recent progress in studies to solve the practical problem of cross-mixing tests has been remarkable in Japan; however, this information was not well presented to clinical laboratory technologists and hospital doctors. Therefore, three specialists have contributed articles on problems of solving clinical and laboratory diagnoses of anti-phospholipid syndrome and acquired hemophilia, both from the clinical setting. These articles show new concrete approaches to carry out blood coagulation tests and their laboratory information.

  10. Acquired loss of red cell Kell antigens.

    PubMed

    Vengelen-Tyler, V; Gonzalez, B; Garratty, G; Kruppe, C; Johnson, C L; Mueller, K A; Marsh, W L

    1987-02-01

    A 19-year-old patient with a long history of idiopathic thrombocytopenic purpura developed a potent antibody against a high-incidence antigen in the Kell blood group system. The direct antiglobulin test on his red cells was negative. His cells exhibited profound depression of Kell blood group antigens, but antigens of other blood groups were normal. Transfusion of incompatible blood was well tolerated and differential agglutination tests, using selected Rh antisera, showed in vivo survival of the transfused red cells for more than 8 weeks. However, the transfused red cells also showed acquired loss of Kell antigens. Five months after the initial findings, Kell-related antibody disappeared and Kell antigens reappeared on his red cells. The patient's serum stored from the initial investigation now reacted with his freshly collected red cells. These data suggest that an environmental agent in the patient's plasma was responsible for the temporary loss of Kell antigens from red cells in his circulation.

  11. Rapid encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Golla, Sunitha; Horkan, Clare; Dogaru, Grigore; Teske, Thomas E; Christopher, Kenneth

    2008-01-01

    Rho (D) immune globulin intravenous (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura. Common side effects of IV RhIG include mild hemolysis, febrile reaction and headache. Significant hemolysis with renal impairment is infrequently noted. A single case of irreversible encephalopathy following IV RhIG has been reported. We report a second case of encephalopathy following an infusion of IV RhIG for treatment of idiopathic thrombocytopenic purpura.

  12. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  13. Harmful and beneficial antibodies in immune thrombocytopenic purpura.

    PubMed Central

    Imbach, P A

    1994-01-01

    Two facts support the definition of idiopathic thrombocytopenic purpura (ITP) as an immune disorder. First, antibodies against platelets, which often appear after a viral infection, provoke the increased elimination of these cells. Viral disease may change the complex immune response of the host at different levels. In chronic ITP, the consequences of the dysregulated immune system are autoantibodies, primarily against platelet glycoprotein IIb/IIIa. Second, pooled immunoglobulins from healthy blood donors may influence the imbalanced immune response in ITP. The initial study dose of 5 x 0.4 g of intact 7S IgG/kg body weight can now be reduced to 2 x 0.4 g/kg body weight in the majority of patients. The possible mechanisms of action of intravenous immune globulin (IVIG) are reviewed and updated in this article. The combination of effects on the humoral and cellular immune responses using IVIG in concert with cytokines may open up new therapeutic possibilities. PMID:8033430

  14. Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

    PubMed Central

    Toshikuni, Nobuyuki; Yamato, Ryumei; Kobashi, Haruhiko; Nishino, Ken; Inada, Nobu; Sakanoue, Ritsuko; Suehiro, Mitsuhiko; Fujimura, Yoshinori; Yamada, Gotaro

    2008-01-01

    Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year-old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB1*0601 and DRB1*0803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP. PMID:18416479

  15. Helicobacter pylori infection and immune thrombocytopenic purpura: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2004-08-01

    Data are accumulating on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on H. pylori infection and ITP in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 278 out of the 482 ITP patients investigated (58%) were positive for H. pylori infection and that the bacterium was eradicated in 88% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that H. pylori eradication in patients with ITP is effective in increasing platelet count. However, because the studies so far published are few, are sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.

  16. Treatment of immune thrombocytopenic purpura: focus on eltrombopag

    PubMed Central

    Rice, Lawrence

    2009-01-01

    Immune thrombocytopenic purpura (ITP) is a relatively common autoimmune disorder in which antibodies are produced to circulating platelets. Symptoms can be mild, but for most patients the risk of severe bleeding is unacceptable and treatment is required. Glucocorticoids followed by splenectomy had been the mainstays of therapy. High dose intravenous immunoglobulin and anti-RhD therapy are available for patients with severe illness, but produce only temporary benefit. Rituximab may provide more durable responses, danazol may be underutilized, and immunosuppressants and cytotoxic agents are less often required. Recently the pathophysiology of ITP has been more clearly elucidated, particularly the importance of decreased production of platelets in most patients and the very blunted rise that occurs in serum thrombopoietin (TPO). The isolation of TPO and better understanding of its role in thrombopoiesis has led to the development of new highly effective treatments. TPO analogs had some successes in treating highly refractory ITP patients but were taken out of development due to TPO-antibody induction. Two second-generation TPO-mimetics, romiplostim and the orally available eltrombopag, have recently been licensed in some territories for the treatment of ITP. Approval of eltrombopag was based on results from Phase II and III placebo-controlled clinical trials and a long-term extension study. About 80% of patients achieve significant increases in platelet count (11% of placebo patients), with reduced bleeding and reduced use of concomitant medications; responses are often durable with no tachyphylaxis. The side effects of eltrombopag are generally mild and not worse than placebo, although there are concerns about hepatic dysfunction, and the potentials for thromboses, marrow reticulin fibrosis, rebound thrombocytopenia and cataracts. This is an important new option for highly refractory patients, and its niche in earlier treatment (and for other thrombocytopenic

  17. Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen.

    PubMed

    Nayak, Manasa K; Singh, Sunil K; Roy, Arnab; Prakash, Vivek; Kumar, Anand; Dash, Debabrata

    2011-10-01

    Tamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signalling machinery has not been elucidated in detail. In the present report we show that tamoxifen is endowed with significant inhibitory property against human platelet aggregation. From a series of in vivo and in vitro studies tamoxifen was found to inhibit almost all platelet functions, prolong tail bleeding time in mouse and profoundly prevent thrombus formation at injured arterial wall in mice, as well as on collagen matrix perfused with platelet-rich plasma under arterial shear against the vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti-platelet/anti-thrombotic agent. PMID:21866300

  18. Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen.

    PubMed

    Nayak, Manasa K; Singh, Sunil K; Roy, Arnab; Prakash, Vivek; Kumar, Anand; Dash, Debabrata

    2011-10-01

    Tamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signalling machinery has not been elucidated in detail. In the present report we show that tamoxifen is endowed with significant inhibitory property against human platelet aggregation. From a series of in vivo and in vitro studies tamoxifen was found to inhibit almost all platelet functions, prolong tail bleeding time in mouse and profoundly prevent thrombus formation at injured arterial wall in mice, as well as on collagen matrix perfused with platelet-rich plasma under arterial shear against the vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti-platelet/anti-thrombotic agent.

  19. Thrombotic microangiopathy as an initial manifestation in HIV patients

    PubMed Central

    Dineshkumar, Thanigachalam; Dhanapriya, Jeyachandran; Jaganathan, Palanivel; Sakthirajan, Ramanathan; Gopalakrishnan, Natarajan; Balasubramaniyan, T.

    2016-01-01

    Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, microvascular thrombosis, and various organ dysfunctions. TMA usually occurs in a more advanced stage of HIV disease. TMA as an initial presenting feature is rare. We here report a male patient who presented with oliguric renal failure. Investigations revealed anemia, thrombocytopenia, schistocytes in peripheral smear, and HIV-positive. Renal biopsy revealed TMA. He was treated with hemodialysis and started on highly active antiretroviral therapy. PMID:27390466

  20. Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma

    PubMed Central

    Kuriyama, Keiko; Kinoshita, Tatsuya; Nagai, Keisuke; Hongyo, Hidenari; Kishimoto, Kentaro; Inoue, Atsuo; Takamura, Manabu; Choi, Soomi

    2016-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma.

  1. THROMBOTIC MICROANGIOPATHY ASSOCIATED WITH OPANA ER INTRAVENOUS ABUSE A Case Report.

    PubMed

    Jabr, Fadi I; Yu, Ling

    2016-01-01

    Thrombotic microangiopathy is characterized by endothelial changes and microvascular stenosis. Several entities such as pregnancy, infection, connective tissue diseases, and drugs are associated with secondary thrombotic microangiopathy. Recently, new reformulation of Opana ER had been associated with thrombotic microangiopathy when injected intravenously. Here, we report the case of a 37-year-old man who developed renal failure and hemolytic anemia secondary to Opana ER intravenous abuse. Renal biopsy pathology was consistent with thrombotic microangiopathy likely caused by Opana ER intravenous abuse. PMID:27169165

  2. Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma

    PubMed Central

    Kuriyama, Keiko; Kinoshita, Tatsuya; Nagai, Keisuke; Hongyo, Hidenari; Kishimoto, Kentaro; Inoue, Atsuo; Takamura, Manabu; Choi, Soomi

    2016-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma. PMID:27635254

  3. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

    Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease. PMID:27478601

  4. Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma.

    PubMed

    Katayama, Daisuke; Kuriyama, Keiko; Kinoshita, Tatsuya; Nagai, Keisuke; Hongyo, Hidenari; Kishimoto, Kentaro; Inoue, Atsuo; Takamura, Manabu; Choi, Soomi

    2016-08-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma. PMID:27635254

  5. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    PubMed

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas.

  6. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    PubMed

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas. PMID:27596376

  7. Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

    SciTech Connect

    Ware, R.; Kinney, T.R.; Rosse, W.

    1985-11-01

    Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a SVI-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.

  8. Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Coleman, Christopher; Nassar, Aziza; McComb, Barbara

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

  9. Pulmonary hyalinizing granuloma associated with idiopathic thrombocytopenic purpura.

    PubMed

    Coleman, Christopher; Nassar, Aziza; McComb, Barbara

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

  10. Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias

    SciTech Connect

    Sugiura, K.; Steiner, M.; Baldini, M.G.

    1980-10-01

    Platelet-associated immunoglobulin was measured by the use of fluorescent anti-1gG antibody. The method is simple, rapid, and sensitive and provides a precise quantitive assay of bound (direct) and free (indirect) 1gG with platelet specificity. We have evaluated this test in 30 normal volunteers and in 50 patients with immune and nonimmune, treated and untreated thrombocytopenias. All patients with immune thrombocytopenias (acute and chronic idiopathic thrombocytopenic purpura and systemic lupus erythematosus) having platelet counts < 100,000/..mu..l had elevated levels of platelet-bound 1gG and 86% had also positive results in the indirect assay. All patients with nonimmunological thrombocytopenias showed normal results in the direct and indirect assay of platelet-associated immunoglobulin. In patients studied repeatedly during the course of their illness, an inverse relation was found between platelet count and level of platelet-bound 1gG. Patients with systemic lupus erythematosus presented clear exceptions to this rule. Investigations of the absorbability of platelet autoantibodies and alloantibodies showed that this assay can readily differentiate between these two antibody species and can also identify specificities of alloantibodies.

  11. Pregnancy and Birth Outcomes among Women with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Wyszynski, Diego F.; Carman, Wendy J.; Cantor, Alan B.; Graham, John M.; Kunz, Liza H.; Slavotinek, Anne M.; Kirby, Russell S.; Seeger, John

    2016-01-01

    Objective. To examine pregnancy and birth outcomes among women with idiopathic thrombocytopenic purpura (ITP) or chronic ITP (cITP) diagnosed before or during pregnancy. Methods. A linkage of mothers and babies within a large US health insurance database that combines enrollment data, pharmacy claims, and medical claims was carried out to identify pregnancies in women with ITP or cITP. Outcomes included preterm birth, elective and spontaneous loss, and major congenital anomalies. Results. Results suggest that women diagnosed with ITP or cITP prior to their estimated date of conception may be at higher risk for stillbirth, fetal loss, and premature delivery. Among 446 pregnancies in women with ITP, 346 resulted in live births. Women with cITP experienced more adverse outcomes than those with a pregnancy-related diagnosis of ITP. Although 7.8% of all live births had major congenital anomalies, the majority were isolated heart defects. Among deliveries in women with cITP, 15.2% of live births were preterm. Conclusions. The results of this study provide further evidence that cause and duration of maternal ITP are important determinants of the outcomes of pregnancy. PMID:27092275

  12. Late Results After Splenectomy in Adult Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Vecchio, Rosario; La Corte, Francesco; Marchese, Salvatore; Cacciola, Rossella R.; Cacciola, Emma

    2015-01-01

    Background: We performed a retrospective study on patients with idiopathic thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in relation to preoperative platelet count. Materials and Methods: Two groups of patients operated on with laparoscopic or open splenectomy for ITP, with a platelet count ≤30,000/μL (study group: 22 patients) and >30,000/μL (control group: 18 patients), respectively, were compared. The two groups were homogeneous in relation to age, sex, length of preoperative steroid therapy, and time interval between diagnosis and surgery (Student t test with P > .1). The results of surgery were evaluated at one year after splenectomy. Positive response to surgery, according to the American Society of Hematologic Guidelines, was considered in patients with a postoperative platelet count ≥100,000/μL or in patients with a postoperative platelet count ≥30,000/μL and a twofold increase in platelet count from baseline, in the absence of bleeding. The postoperative platelet count increase rate was statistically related to preoperative platelet count in both the study and control groups. Statistical analysis was performed using the Student's t test for independent sample and the Pearson correlation in a 2-tailed test. Results: No relationship between preoperative platelet count and postoperative platelet percent increase was observed in the control group (r = –0.41; P = .089), whereas a significant negative correlation (r = –0.68; P = .0004) was found in the study group. Conclusions: A higher increase of postoperative percent platelet count may be predicted in patients with a low preoperative platelet count. PMID:25848175

  13. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    SciTech Connect

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

  14. Platelet-associated complement C3 in immune thrombocytopenic purpura

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1982-05-01

    Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associatd IgG (PA-lgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP wre classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studies showed reduced survival times of 1.5-2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteriod therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classifiation by Coombs' testing in immune hemolytic anemia.

  15. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates.

    PubMed

    Sola-Visner, Martha C; Christensen, Robert D; Hutson, Alan D; Rimsza, Lisa M

    2007-04-01

    Thrombocytopenia is frequent among sick neonates, but little is known about its underlying mechanisms. It is known, however, that neonatal megakaryocytes are smaller and of lower ploidy than their adult counterparts and that smaller megakaryocytes produce fewer platelets than larger, more polyploid, megakaryocytes. We hypothesized that neonatal megakaryocytes would not increase their size in response to thrombocytopenia, thus limiting the ability of neonates to mount a response. To test this, we obtained marrow specimens from thrombocytopenic and nonthrombocytopenic neonates and adults. Megakaryocytes were immunohistochemically stained, quantified using an eyepiece reticle, and measured using an image analysis system with incorporated electronic micrometer. We found that, after adjusting for differences in cellularity, neonates and adults had similar megakaryocyte concentrations. When samples from the same sources were compared (tibial clot and vertebral body sections in neonates, iliac crest biopsies in adults), there were also no differences in megakaryocyte concentration between thrombocytopenic and nonthrombocytopenic subjects. The megakaryocyte diameter, however, was greater in adults than in neonates (19.4 +/- 3.0 versus 15.3 +/- 1.7 microm, p<0.0001). Thrombocytopenic adults also had a higher proportion of large megakaryocytes than nonthrombocytopenic adults (p<0.001). This was not observed among thrombocytopenic neonates, suggesting a developmental limitation in their ability to increase megakaryocyte size. PMID:17515875

  16. A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients.

    PubMed

    Fujii, T; Shimomura, T; Fujimoto, T T; Kimura, A; Fujimura, K

    2000-03-15

    Recent studies have shown that reticulated platelets stained with Thiazole Orange (T.O.) are useful markers for thrombopoiesis. The percentage of T.O. positive platelets tends to be inconsistent using the original method, especially when the peripheral blood platelet count is very low. We measured T.O. positive platelet levels in patients with severe thrombocytopenic disorders, using concentrated platelet-rich plasma and carrying out a two-color analysis involving T.O. and an anti-glycoprotein IIb/IIIa monoclonal antibody. This method allowed us to obtain consistent T.O. positive platelet rates in patients with thrombocytopenia whose platelet counts were below 20 approximately 30x10(9)/l. By this method, the T.O. positive rates of platelets from idiopathic thrombocytopenic purpura patients were found to be significantly higher than in the control group. The T.O. positive rates of other thrombocytopenic disorders were similar to those of the control group. These results are consistent with those previously reported. We conclude that our technique of measuring of T.O. positive platelets using platelet-rich plasma is useful for analyzing severe thrombocytopenic disorders.

  17. Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease

    PubMed Central

    Sengupta, Dibyendu; Kahn, Andrew M.; Kung, Ethan; Moghadam, Mahdi Esmaily; Shirinsky, Olga; Lyskina, Galina A.; Burns, Jane C.; Marsden, Alison L.

    2016-01-01

    Kawasaki disease (KD) is the leading cause of acquired heart disease in children and can result in life-threatening coronary artery aneurysms in up to 25 % of patients. These aneurysms put patients at risk of thrombus formation, myocardial infarction, and sudden death. Clinicians must therefore decide which patients should be treated with anticoagulant medication, and/or surgical or percutaneous intervention. Current recommendations regarding initiation of anticoagulant therapy are based on anatomy alone with historical data suggesting that patients with aneurysms ≥8 mm are at greatest risk of thrombosis. Given the multitude of variables that influence thrombus formation, we postulated that hemodynamic data derived from patient-specific simulations would more accurately predict risk of thrombosis than maximum diameter alone. Patient-specific blood flow simulations were performed on five KD patients with aneurysms and one KD patient with normal coronary arteries. Key hemodynamic and geometric parameters, including wall shear stress, particle residence time, and shape indices, were extracted from the models and simulations and compared with clinical outcomes. Preliminary fluid structure interaction simulations with radial expansion were performed, revealing modest differences in wall shear stress compared to the rigid wall case. Simulations provide compelling evidence that hemodynamic parameters may be a more accurate predictor of thrombotic risk than aneurysm diameter alone and motivate the need for follow-up studies with a larger cohort. These results suggest that a clinical index incorporating hemodynamic information be used in the future to select patients for anticoagulant therapy. PMID:24722951

  18. Thrombotic microangiopathy associated with tacrolimus in lung transplantation.

    PubMed

    Reig Mezquida, Juan Pablo; Jover, Amparo Solé; Ansótegui Barrera, Emilio; Escrivá Peiró, Juan; Pastor Colom, Maria Desamparados; Pastor Guillem, Juan

    2015-05-01

    Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients.

  19. Clinical biomarkers and management of post thrombotic syndrome.

    PubMed

    Biondi, Antonio; Strano, Giuseppe; Ruggeri, Luca; Vadala, Salvatore; Tropea, Alessandro; Basile, Francesco

    2010-01-01

    The post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterized by chronic, persistent pain, swelling and other signs in the affected limb. PTS is common, burdensome and costly. It is likely to increase in prevalence, since despite widespread use of and improvements in the efficacy of thromboprophylaxis, the incidence of DVT has not decreased over time. Preventing ipsilateral recurrence of DVT, by ensuring an adequate duration and intensity of anticoagulation for the initial DVT and by prescribing situational thromboprophylaxis after discontinuation of oral anticoagulants, is likely to reduce the risk of developing PTS. Pending the results of ongoing studies, stockings are recommended in patients with persistent symptoms or swelling after DVT. Future research should focus on standardizing criteria for PTS diagnosis, identification of DVT patients at high risk for PTS, and rigorously evaluating the effectiveness of stockings, thrombolysis, and venoactive drugs in preventing or treating PTS. PMID:20036921

  20. Extra-Renal Manifestations of Complement-Mediated Thrombotic Microangiopathies

    PubMed Central

    Hofer, Johannes; Rosales, Alejandra; Fischer, Caroline; Giner, Thomas

    2014-01-01

    Thrombotic microangiopathies (TMA) are rare but severe disorders, characterized by endothelial cell activation and thrombus formation leading to hemolytic anemia, thrombocytopenia, and organ failure. Complement over activation in combination with defects in its regulation is described in an increasing number of TMA and if primary for the disease denominated as atypical hemolytic-uremic syndrome. Although TMA predominantly affects the renal microvasculature, extra-renal manifestations are observed in 20% of patients including involvement of the central nerve system, cardiovascular system, lungs, skin, skeletal muscle, and gastrointestinal tract. Prompt diagnosis and treatment initiation are therefore crucial for the prognosis of disease acute phase and the long-term outcome. This review summarizes the available evidence on extra-renal TMA manifestations and discusses the role of acute and chronic complement activation by highlighting its complex interaction with inflammation, coagulation, and endothelial homeostasis. PMID:25250305

  1. Thrombotic manifestations in SAPHO syndrome. Review of the literature.

    PubMed

    Carranco-Medina, Tatiana Elizabeth; Hidalgo-Calleja, Cristina; Calero-Paniagua, Ismael; Sánchez-González, María Dolores; Quesada-Moreno, Alba; Usategui-Martín, Ricardo; Pérez-Garrido, Laura; Gómez-Castro, Susana; Montilla-Morales, Carlos Alberto; Martínez-González, Olga; Del Pino-Montes, Javier

    2015-01-01

    SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted.

  2. "Unusual Cause Of Tophi With Renal Thrombotic Microangiopathy".

    PubMed

    Sahu, Kamal Kant; Law, Arjun Datt; Kumar, Ganesh; Dhir, Varun; Naseem, Shano; Nada, Ritambhra; Varma, Subhash Chander; Malhotra, Pankaj

    2016-06-01

    Chronic neutrophilic leukemia (CNL) is a rare entity amongst myeloproliferative neoplasms (MPNs). The classical presentation of CNL is with splenomegaly, mature neutrophilic leucocytosis and hyperuricemia. We herein report a case who presented with symptoms of acute gouty arthritis. Physical examination showed typical red, tender tophi in the right hand, right foot and both pinnae suggesting an acute episode of gout. During evaluation, moderate splenomegaly, mature neutrophilia, hyperuricemia and sub-nephrotic range range proteinuria were noted. Bone marrow examination and kidney biopsy was done. Final diagnosis of CNL with acute gouty arthritis and chronic renal thrombotic microangiopathy (TMA) was made. Although hyperuricemia is a common finding in MPNs but presentation of our case with symptoms of acute tophi and chronic TMA is atypical. PMID:27408367

  3. Scorpion envenomation-induced acute thrombotic inferior myocardial infarction.

    PubMed

    Baykan, Ahmet Oytun; Gür, Mustafa; Acele, Armağan; Şeker, Taner; Çaylı, Murat

    2016-01-01

    The occurrence of a serious cardiac emergency following scorpion envenomation has rarely been reported and, when so, mostly presented as non-ST segment elevation myocardial infarction, cardiogenic shock, or myocarditis. Possible mechanisms include imbalance in blood pressure and coronary vasospasm caused by the combination of sympathetic excitation, scorpion venom-induced release of catecholamines, and the direct effect of the toxin on the myocardium. We report a case of a 55-year-old man who presented with acute inferior wall myocardial infarction (MI) within 2 h of being stung by a scorpion. Coronary angiogram revealed total thrombotic occlusion of the left circumflex artery, which was treated successfully with glycoprotein IIb/IIIa inhibitor, thrombus aspiration, antivenom serum, and supportive therapy. Therefore, life-threatening MI can complicate the clinical course during some types of scorpion envenomation and should be managed as an acute coronary syndrome. PMID:26875137

  4. Acute Thrombotic Mesenteric Ischemia: Primary Endovascular Treatment in Eight Patients

    SciTech Connect

    Gagniere, Johan; Favrolt, Gregory; Alfidja, Agaiecha; Kastler, Adrian; Chabrot, Pascal; Cassagnes, Lucie; Buc, Emmanuel; Pezet, Denis; Boyer, Louis

    2011-10-15

    Introduction: The purpose of this study was to evaluate our experience with initial percutaneous transluminal angioplasty (PTA) {+-} stenting as valuable options in the acute setting. Methods: Between 2003 and 2008, eight patients with abdominal angio-MDCT-scan proven thrombotic AMI benefited from initial PTA {+-} stenting. We retrospectively assessed clinical and radiological findings and their management. Seven patients presented thrombosis of the superior mesenteric artery, and in one patient both mesenteric arteries were occluded. All patients underwent initial PTA and stenting, except one who had balloon PTA alone. One patient was treated by additional in situ thrombolysis. Results: Technical success was obtained in all patients. Three patients required subsequent surgery (37.5%), two of whom had severe radiological findings (pneumatosis intestinalis and/or portal venous gas). Two patients (25%) died: both had NIDD, an ASA score {>=}4, and severe radiologic findings. Satisfactory arterial patency was observed after a follow-up of 15 (range, 11-17) months in five patients who did not require subsequent surgery, four of whom had abdominal guarding but no severe CT scan findings. One patient had an ileocecal stenosis 60 days after the procedure. Conclusions: Initial PTA {+-} stenting is a valuable alternative to surgery for patients with thrombotic AMI even for those with clinical peritoneal irritation signs and/or severe radiologic findings. Early surgery is indicated if clinical condition does not improve after PTA. The decision of a subsequent surgery must be lead by early clinical status reevaluation. In case of underlying atherosclerotic lesion, stenting should be performed after initial balloon dilatation.

  5. Plasma microRNA profiling of pediatric patients with immune thrombocytopenic purpura.

    PubMed

    Bay, Ali; Coskun, Enes; Oztuzcu, Serdar; Ergun, Sercan; Yilmaz, Fatih; Aktekin, Elif

    2014-06-01

    Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.

  6. The endothelium as the common denominator in malignant hypertension and thrombotic microangiopathy.

    PubMed

    Mathew, Roy O; Nayer, Ali; Asif, Arif

    2016-04-01

    The endothelium plays a pivotal role in vascular biology. The endothelium is the primary site of injury in thrombotic microangiopathies including malignant hypertension. Endothelial injury in thrombotic microangiopathies is the result of increased shear stress, toxins, and/or dysregulated complement activation. Endothelial injury can lead to microvascular thrombosis resulting in ischemia and organ dysfunction, the clinical hallmarks of thrombotic microangiopathies. Currently, available therapies target the underlying mechanisms that lead to endothelial injury in these conditions. Ongoing investigations aim at identifying drugs that protect the endothelium. PMID:26778772

  7. Association between Thrombophilia and the Post-Thrombotic Syndrome

    PubMed Central

    Kahn, Susan R.

    2013-01-01

    The post thrombotic syndrome (PTS) is a chronic condition that develops in 20%–40% of deep vein thrombosis (DVT) patients. While risk factors that predispose to the development of venous thromboembolism (VTE) are widely known, factors that influence the development of PTS after DVT have not been well elucidated. Over 10% of the general population is affected by one or more identifiable inherited thrombophilias which have been shown to underlie at least 1/3 of cases of VTE. The various thrombophilias are important risk factors for VTE, but it is unknown whether they also increase the risk for development of PTS. We performed a review of studies that have reported on the association between thrombophilia and the development of PTS in populations of patients with DVT and with chronic venous ulcers. Studies vary with regards to the definition of PTS, study design, follow-up period, and present conflicting results. Based on these results, the question of whether thrombophilia predisposes to the development of PTS remains unanswered. PMID:23762560

  8. Severe central nervous system thrombotic events in hemoglobin Sabine patient.

    PubMed

    Pavlovic, Sonja; Kuzmanovic, Milos; Urosevic, Jelena; Poznanic, Jelena; Zoranovic, Tamara; Djordjevic, Valentina; Rasovic, Nada; Bunjevacki, Gordana; Cvorkov-Drazic, Milica; Colovic, Milica

    2004-01-01

    Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype. Extremely high level of Hb F and rather mild anemia in our patient could be partially explained by the presence of G gamma Xmn I polymorphism. This case of Hb Sabine, unlike all other reported to date, shows extremely severe thromboembolic complications. It is our opinion that the hypercoagulable state described in thalassemia is not the only factor responsible for this specific clinical state. The presence of MTHFR C677T mutation in heterozygous state found in our patient and unstable Hb Sabine molecules could contribute to development of thromboembolic phenomena. However, it remains unclear whether other factors participate in pathogenesis of the disease. In this paper we emphasize different genetic background of father and son both affected with Hb Sabine, but with markedly different severity of the disease.

  9. Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. 1946.

    PubMed

    2016-01-01

    This paper, by one of the legends of hematology, William Dameshek, and his colleague Edward Miller, is from the inaugural issue of Blood. By studying bone marrow specimens from controls, patients with acute or chronic immune thrombocytopenia, or patients with other thrombocytopenic disorders, the authors concluded that, in idiopathic thrombocytopenic purpura (ITP), production of platelets from megakaryocytes is defective, even while marrow megakaryocytes are greatly increased in number. This defect resolved after splenectomy. The authors appropriately credit E. Frank with having proposed defective platelet production from megakaryocytes in ITP in 1915. The idea that platelet production was defective in ITP was superseded or ignored for decades, but it has now been validated by the therapeutic effectiveness of the thrombopoietin mimetics in ITP.

  10. Cerebral venous thrombosis after immune thrombocytopenic purpura and anti-D immune globulin therapy.

    PubMed

    Kayyali, Husam R; Abdelmoity, Ahmed T; Morriss, M Craig; Graf, William D

    2008-03-01

    Cerebral venous thrombosis has multiple etiologies and a wide variety of clinical manifestations. This article reports on a young girl who developed cerebral venous thrombosis after intravenous anti-D immune globulin therapy for immune thrombocytopenic purpura. In this case, venous infarction was manifested by an unusual pattern of restricted diffusion limited to the corpus callosum. The cause of cerebral venous thrombosis in this patient may be related to both immune thrombocytopenia and immunoglobulin therapy.

  11. Rapid irreversible encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Christopher, Kenneth; Horkan, Clare; Barb, Ilie T; Arbelaez, Christian; Hodgdon, Travis A; Yodice, Paul C

    2004-11-01

    Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant hemolysis with renal impairment following IV RhIG has been reported. We report a case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for treatment of ITP.

  12. Pathogenesis, laboratory, and clinical characteristics of Helicobacter pylori-associated immune thrombocytopenic purpura.

    PubMed

    Franchini, Massimo; Plebani, Mario; Montagnana, Martina; Veneri, Dino; Lippi, Giuseppe

    2010-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disease mediated by autoantibodies against platelet glycoproteins. This hemorrhagic disorder may be primary or secondary to various illnesses, including lymphoproliferative, autoimmune, or infectious diseases. Among the latter causes, there is increasing laboratory and clinical evidence that documents a pathogenic role of Helicobacter pylori infection in ITP. The aim of this review is to analyze the current knowledge on the pathogenic, diagnostic, clinical, and therapeutic characteristics of H. pylori-associated ITP.

  13. [Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus--a case report].

    PubMed

    Prusek, Katarzyna; Deja, Grażyna; Jarosz-Chobot, Przemysława

    2010-01-01

    The relation between type 1 diabetes mellitus and autoimmune thyroid diseases is well known. In the pathogenesis of both diseases, chronic autoimmunization plays an essential role. Specific autoantibodies are also responsible for the onset of idiopathic thrombocytopenic purpura. In the paper we present a case of an 11-year-old girl with insulin dependent diabetes in whom the idiopathic thrombocytopenic purpura without bleeding diathesis has been newly diagnosed. The patient had positive titres of thyroid autoantibodies, whilst she did not suffer from thyroid dysfunction. Due to inefficiency of intravenous gammaglobulins the patient was treated with a steroid therapy, which elevated the platelet counts to safe levels. However, the episodes of hyperglycemia have appeared as a side effect. The insulin therapy was modified and the girl was released in a good condition. In this case report, consideration should be given to the wide range of autoimmune diseases that can accompany type one diabetes mellitus--not only can we observe immune diabetic markers, but also thyroid autoantibodies and anti-platelet antibodies. Particular therapeutic dilemmas resulting in a difficult decision on steroid therapy while treating a diabetic patient with idiopathic thrombocytopenic purpura are also presented. PMID:21092704

  14. Flow cytometric analysis of anti-platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed

    Latorraca, A; Lanza, F; Moretti, S; Ferrari, L; Reverberi, R; Galluccio, L; Castoldi, G

    1994-01-01

    Anti-platelet antibody measurement may be important in defining the pathogenesis of thrombocytopenic states. In this paper we compared three anti-human immunoglobulin reagents by using them to detect anti-platelet antibodies on the platelet surface and in the serum of 14 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 22 thrombocytopenic disorders. Samples were analyzed by both flow cytometry and a fluorescence microscope. In ITP patients, the direct test was positive in 50% of the cases, while the indirect technique proved to be positive in a slightly higher number of those tested (56%). Furthermore, the number of positive cases was similar for the three reagents used in this study, although the mean percentage of positive platelets was higher for the kappa/lambda monoclonal reagent. These data further support the sensitivity and reproducibility of flow cytometry analysis, which was capable of detecting antiplatelet antibodies in all patients with transfused Cooley's disease (regarded as positive control), as well as in a significant number of patients with ITP or related diseases. On the basis of the data presented here, definitive proof regarding the presence of anti-platelet antibodies in patients with thrombocytopenia still has to be found, and further studies are needed in order to ascertain the autoimmune nature of these disorders. PMID:7926978

  15. Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates.

    PubMed

    Kulshrestha, Mudit; Sola-Visner, Martha; Widness, John A; Veng-Pedersen, Peter; Mager, Donald E

    2015-01-01

    Neonatal thrombocytopenia affects 22-35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates. PMID:25362135

  16. Special Blood Donation Procedures

    MedlinePlus

    ... type of abnormal antibody formation), and thrombotic thrombocytopenic purpura (a rare clotting disorder). In cytapheresis, excess numbers ... generally does not cure them. However, thrombotic thrombocytopenic purpura can be cured with apheresis. Directed or designated ...

  17. What Causes Thrombocytopenia?

    MedlinePlus

    ... Transfusion Disseminated Intravascular Coagulation Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... low platelet count. Two examples are thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). TTP is ...

  18. Are burn patients really at risk for thrombotic events?

    PubMed

    Satahoo, Shevonne S; Parikh, Punam P; Naranjo, Daniel; Davis, James S; Duncan, Robert C; Pizano, Louis R; Namias, Nicholas; Schulman, Carl I

    2015-01-01

    There continues to be debate about the routine use of deep vein thrombosis (DVT) prophylaxis in burn patients. The concern is that routine prophylaxis may lead to adverse events. The debate hinges on the incidence of DVT and its relation to the risk-benefit ratio. This study seeks to estimate the true rate of DVT in burn patients, and to evaluate possible risk factors to its development. The Nationwide Inpatient Sample was queried for all patients with age ≥18 years with ICD-9 codes for burn injuries. Demographic data, comorbidities, burn data, length of stay, total charges, procedures, presence of central venous catheter, and mortality were recorded. Patients were classified based on the presence of DVT. Student's t-test, χ test, and logistic regression were performed. 36,638 burn patients were identified. DVT rate was 0.8%. Patients with DVT were older, had longer hospitalizations, more procedures, and higher charges. On logistic regression, black race, TBSA ≥20%, history of previous venous thrombotic events, blood transfusion, and mechanical ventilation were the significant factors associated with DVT. Patients with DVT were almost twice as likely to die during the admission (P = .011). This is the largest series to date examining the risk factors for DVT in burn patients. DVT developed in approximately 0.8% of burn patients. Black race, TBSA ≥20%, blood transfusions, and mechanical ventilation were associated with approximately 2-fold odds of developing DVT. Identification of these additional risk factors may allow targeted patient prophylaxis. Additionally, patients with DVT incurred higher total charges and longer hospitalization.

  19. Severe Thrombotic and Bleeding Complications in a Baby with Heterozygous Factor V Leiden and Acquired von Willebrand Disease on ECMO

    PubMed Central

    Bilen, Ozlem; Loftis, Laura; Teruya, Jun

    2011-01-01

    Abstract: We aim to present the case of a 5-week-old girl with severe respiratory failure placed on veno-venous extracorporeal membrane oxygenation (ECMO) that was then switched to veno-arterial ECMO. She required up to 60 units/kg/hr of heparin to keep her heparin level within the target range at .3–.7 units/mL. During the ECMO course, substantial thrombus formation was observed within the venous site of the ECMO cannula, which led to two circuit changes on ECMO day 9 and day 20. On ECMO day 15, she was noticed to have purpuric lesions on her chest and her right hand with no obvious arterial or venous clot detected by Doppler ultrasound. She was also noted to have remarkable hemolysis as the plasma free hemoglobin levels were substantially elevated up to 700 mg/dL. She was noted to have continuous oozing from the catheter insertion sites despite adequate underlying coagulation status. Her subsequent platelet function analysis, the thromboelastography, and thromboelastography platelet mapping suggested substantial platelet dysfunction. Her von Willebrand panel revealed absence of high molecular weight multimers. Further coagulation workup was prompted which revealed heterozygosity for factor V Leiden. The patient developed severe pulmonary hemorrhages and ECMO was discontinued on day 40. PMID:21848174

  20. Unusual presentation of pulmonary tumor thrombotic microangiopathy with no detectable primary tumor.

    PubMed

    Seppala, N; Cala, A; Klebe, S

    2009-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Its development is linked to the presence of pulmonary tumor microemboli (PTM) and should be suspected in patients with unexplained dyspnea, especially in the presence of adenocarcinoma. PTTM presents in a similar fashion to respiratory disease such as pulmonary embolism, pulmonary hypertension or pneumonia and is usually only diagnosed post-mortem. We report a case of PTTM identified ante-mortem by bronchial biopsy in an 82-year-old woman presenting with a clinical picture of atypical pneumonia. Autopsy confirmed PTTM, from an unknown primary neoplasm.

  1. Renal Thrombotic Microangiopathy Associated with the Use of Bortezomib in a Patient with Multiple Myeloma

    PubMed Central

    Van Keer, Jan; Delforge, Michel; Dierickx, Daan; Peerlinck, Kathelijne; Lerut, Evelyne; Sprangers, Ben

    2016-01-01

    Bortezomib is a first-generation proteasome inhibitor used in the treatment of multiple myeloma (MM). A few reports have linked bortezomib exposure with the development of thrombotic microangiopathy (TMA). We describe a case of biopsy-proven renal thrombotic microangiopathy associated with the use of bortezomib in a 51-year-old man with IgG lambda MM. To our knowledge, this is the first biopsy-proven case. In addition, reexposure to bortezomib 18 months later was associated with recurrence of TMA. This supports a possible causal role of bortezomib. The exact mechanisms remain to be elucidated. PMID:27293920

  2. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus.

    PubMed

    Culquichicón-Sánchez, Carlos; Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-01-01

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m(2) (P75). A biochemical analysis showed 1×10(9) platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient's glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin. PMID:27026836

  3. Maternal anti-HLA class I antibodies are associated with reduced birth weight in thrombocytopenic neonates.

    PubMed

    Dahl, J; Husebekk, A; Acharya, G; Flo, K; Stuge, T B; Skogen, B; Straume, B; Tiller, H

    2016-02-01

    In this comparative cross-sectional study, possible associations between maternal anti-HLA class I antibodies and birth weight in neonatal thrombocytopenia are explored. Although commonly detected in pregnancies and generally regarded as harmless, it has been suggested that such antibodies might be associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT). As a link between FNAIT due to human platelet antigen 1a-specific antibodies and reduced birth weight in boys has previously been demonstrated, we wanted to explore whether maternal anti-HLA class I antibodies might also affect birth weight. To examine this, suspected cases of FNAIT referred to the Norwegian National Unit for Platelet Immunology during the period 1998-2009 were identified. Pregnancies where the only finding was maternal anti-HLA class I antibodies were included. An unselected group of pregnant women participating in a prospective study investigating maternal-fetal hemodynamics at the University Hospital North Norway during the years 2006-2010 served as controls. Twenty-nine percent of controls had anti-HLA class I antibodies. The thrombocytopenic neonates had a significantly lower adjusted birth weight (linear regression, P=0.036) and significantly higher odds of being small for gestational age (OR=6.72, P<0.001) compared with controls. Increasing anti-HLA class I antibody levels in the mother were significantly associated with lower birth weight and placental weight among thrombocytopenic neonates, but not among controls. These results indicate that maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduced fetal growth. Further studies are needed to test if placental function is affected.

  4. [Protocol for the study and treatment of immune thrombocytopenic purpura (ITP). ITP-2010].

    PubMed

    Monteagudo, E; Fernández-Delgado, R; Sastre, A; Toll, T; Llort, A; Molina, J; Astigarraga, I; Dasí, M A; Cervera, A

    2011-06-01

    Primary immune thrombocytopenia (ITP), formerly known as immune thrombocytopenic purpura, is a disease in which clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of ITP in children based on current guidelines, literature review, clinical trials and member consensus. The primary objective was to lessen clinical variability in diagnostic and therapeutic procedures in order to obtain best clinical results with minimal adverse events and good quality of life.

  5. Pulmonary hyalinizing granuloma. Bilateral pulmonary nodules associated with chronic idiopathic thrombocytopenic purpura.

    PubMed

    Satti, Mohamed B; Batouk, Abdelnasir A; Abdelaziz, Muntasir M; Ahmad, Mohamed F; Abdelaal, Mohamed A

    2005-09-01

    We report a case of a 30-year-old female who had been treated periodically with steroids for idiopathic thrombocytopenic purpura ITP over the last 10 years. Recently, during the course of investigation, she was found to have incidental asymptomatic multiple pulmonary nodules on chest CT. Following a needle biopsy to exclude malignancy, 2 nodules were excised and were histologically confirmed as pulmonary hyalinizing granuloma PHG. The remaining 2 nodules regressed on increasing her dose of steroids. The case is discussed with emphasis on the histological and radiological differential diagnosis, in addition to including ITP among the spectrum of immunologic conditions associated with PHG. PMID:16155671

  6. Surgical treatment of chronic idiopathic thrombocytopenic purpura: results in 107 cases

    SciTech Connect

    Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.

    1986-07-01

    Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.

  7. Role of myeloid human cytomegalovirus infection in children's idiopathic thrombocytopenic purpura.

    PubMed

    Ding, Yan; Zhao, Lei; Mei, Hong; Zhang, Shu-Ling; Huang, Zhi-Hua

    2007-01-01

    This project explores the specificity of myeloid human cytomegalovirus (HCMV) infection in pathogenesis of idiopathic thrombocytopenic purpura (ITP). Eighty-one subjects with ITP were observed. HCMV early antigen and related myeloid cells in bone marrow, and platelet, HCMV IgM, and IgG in blood were tested. The results presented potent evidence that myeloid HCMV infection is a specific factor in children's ITP: patients of ITP with myeloid HCMV infection had a tendency for exacerbation, refractoriness, and chronic advance. However, HCMV did not affect the quantity of megakaryocyte, which showed the complicated relationships between HCMV and ITP.

  8. Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience

    PubMed Central

    McGuckin, S; Westwood, J-P; Webster, H; Collier, D; Leverett, D; Scully, M

    2014-01-01

    Background Plasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group. Study Design and Methods We reviewed all PEX procedures over a 72-month period, following the exclusive introduction of solvent–detergent double viral-inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK). We documented allergic reactions to plasma, citrate reactions, complications relating to central venous access insertion and venous thrombotic events (VTE) in 155 patient episodes and >2000 PEX procedures. Results The overall complication rate was low. Allergic plasma reactions occurred in 6·45% of the cohort with only one episode of acute anaphylaxis. Similarly, VTEs were 6·45%, not significantly greater than in medical patients receiving thromboprophylaxis, despite added potential risk factors in TTP. Citrate reactions were the most frequent complication documented, but toxicity was significantly reduced by administration of further calcium infusions during the PEX procedure. There were no serious central line infections and no catheter thrombosis. Conclusion Our data confirms that PEX continues to be a life-saving procedure in the acute TTP setting and, the procedure was not associated with an increased mortality and limited morbidity. PMID:24117855

  9. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy

    PubMed Central

    Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-01-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 109/L to 43.0 × 109/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM α-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  10. [Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura].

    PubMed

    Sagawa, Morihiko; Takao, Masaki; Nogawa, Shigeru; Mizuno, Masafumi; Murata, Mitsuru; Amano, Takahiro; Koto, Atsuo

    2003-10-01

    In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.

  11. Extrinsic blood coagulation pathway and risk factors for thrombotic events in patients with essential thrombocythemia.

    PubMed

    Stankowska, Katarzyna; Gadomska, Grażyna; Boinska, Joanna; Michalska, Małgorzata; Bartoszewska-Kubiak, Alicja; Rość, Danuta

    2016-05-31

    INTRODUCTION    The clinical course of essential thrombocythemia (ET) is varied, and some patients do not exhibit any clinical signs of the disease at the time of diagnosis. The most frequent complications that occur during the course of ET are hemostasis abnormalities manifesting as hemorrhagic or thrombotic events. The mechanism of thrombotic events in patients with ET is complex and not fully understood. OBJECTIVES    The aim of the study was to evaluate the concentration and activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI), depending on the most important risk factors of thrombotic complications (age >60 years, history of thrombotic episodes, presence or absence of the JAK2 V617F mutation, and increased leukocyte count). PATIENTS AND METHODS    The study group included 113 patients with diagnosed ET, and the control group, 30 healthy volunteers matched for age and sex. The concentration and activity of TF and TFPI were measured using enzyme-linked immunosorbent assays. RESULTS    Patients with ET had a significantly higher activity and concentration of TF and increased activity of TFPI, as compared with controls. The analysis of the studied parameters in relation to risk factors revealed that patients with ET with a history of thrombotic events had a significantly higher concentration of TF, and patients with the JAK2 V617F mutation had a lower TFPI activity, as compared with patients without the mutation. CONCLUSIONS    Our study showed that in patients with ET who have a history of thrombosis or the JAK2 V617F mutation, the enhanced risk of thrombosis may result from an increased TF concentration or decreased TFPI activity. PMID:27243342

  12. Acquired color vision deficiency.

    PubMed

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  13. Hospital-acquired pneumonia

    MedlinePlus

    ... tends to be more serious than other lung infections because: People in the hospital are often very sick and cannot fight off ... prevent pneumonia. Most hospitals have programs to prevent hospital-acquired infections.

  14. Acquired Cerebral Trauma: Epilogue.

    ERIC Educational Resources Information Center

    Bigler, Erin D., Ed.

    1988-01-01

    The article summarizes a series of articles concerning acquired cerebral trauma. Reviewed are technological advances, treatment, assessment, potential innovative therapies, long-term outcome, family impact of chronic brain injury, and prevention. (DB)

  15. [Acquired haemophilia (acquired factor VIII inhibitor)].

    PubMed

    Ceresetto, José M; Duboscq, Cristina; Fondevila, Carlos; Tezanos Pinto, Miguel

    2015-01-01

    Acquired haemophilia is a rare disorder. The clinical picture ranges from mild ecchymosis and anaemia to life threatening bleeding in up to 20% of patients. The disease is produced by an antibody against Factor VIII and it usually occurs in the elderly, with no previous history of a bleeding disorder. It can be associated to an underlying condition such as cancer, autoimmune disorders, drugs or pregnancy. It has a typical laboratory pattern with isolated prolonged activated partial thromboplastin time (aPTT) that fails to correct upon mixing tests with normal plasma and low levels of factor VIII. Treatment recommendations are based on controlling the acute bleeding episodes with either bypassing agent, recombinant activated factor VII or activated prothrombin complex concentrate, and eradication of the antibody with immunosuppressive therapy.

  16. Thrombotic microangiopathy and human immunodeficiency virus in the era of eculizumab.

    PubMed

    Jin, Anna; Boroujerdi-Rad, Laleh; Shah, Gaurang; Chen, Joline L T

    2016-08-01

    Thrombotic microangiopathies (TMAs) include thrombotic thromobocytopenic purpura and hemolytic uremic syndrome (HUS). Among these conditions, atypical HUS is now recognized to be a disease of alternative complement pathway dysregulation. Eculizumab is a recombinant humanized monoclonal antibody that binds to the complement protein C5 and prevents the cleavage of C5 to C5a and C5b. Eculizumab has been used as a novel treatment for complement-mediated TMA. We present a case of a patient with human immunodeficiency virus infection who developed TMA and was successfully treated with eculizumab. The effect of long-term treatment with this new medication is unknown, and further studies are needed to establish guidelines in the management of this condition. PMID:27478600

  17. Possible episodes that trigger thrombotic events in patients with antiphospholipid syndrome.

    PubMed

    Suzuki, K; Hidaka, T; Shinohara, T; Matsumoto, M; Okada, M; Kataharada, K; Ohsuzu, F

    2000-03-01

    Abstract The presence of antiphospholipid antibodies and/or lupus anticoagulant (LA) increase the risk of thrombosis, while the onset of thrombosis is usually sudden. The objective of this study was to determine whether or not some episodes triggered thrombotic events in patients possessing antiphospholipid antibodies. Fifteen patients who presented with thrombosis (primary antiphospholipid syndrome (APS), six cases; secondary APS, nine cases) were retrospectively examined to discover whether or not any specific episodes occurred prior to a total of 21 thrombotic events. In five events occurring in five female patients, specific episodes were identified, including the wearing of tight underwear, dehydration due to fever and standing in hot and humid weather, fever following the extraction of a carious tooth, steroid pulse therapy, toxemia during pregnancy, and intrauterine fetal death. To prevent the occurrence of thrombosis in patients possessing antiphospholipid antibodies, it appears to be important to avoid such triggering episodes and also to reduce the risk factors for thrombosis. PMID:24383529

  18. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study

    PubMed Central

    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-01-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequently, the clinical features of ITP children with or without rotavirus infection were compared. The results indicated that ITP children with rotavirus infection were significantly younger, showed significantly decreased mean platelet volume (MPV) levels and presented a significantly higher frequency of bleeding score of 3 against ITP children without rotavirus infection. In conclusion, these findings suggest that rotavirus serves a causative role in ITP.

  19. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    García-Méndez, Jorge; Carrillo-Casas, Erika M.; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis. PMID:27313917

  20. The cost of treating immune thrombocytopenic purpura using intravenous Rh immune globulin versus intravenous immune globulin.

    PubMed

    Sandler, S G; Novak, S C; Roland, B

    2000-03-01

    Multiple factors, including efficacy, toxicity and cost, may influence the decision to treat immune thrombocytopenic purpura (ITP) with intravenous immune globulin (IVIG) or intravenous Rho (D) immune globulin (IV RhIG). We conducted a survey of 50 hospitals in 31 states to determine the costs for treating ITP using conventional doses for IVIG or IV RhIG, based on package insert recommendations. The average cost for a dose of IVIG ($2,771) was 71.7% ($1,157) more than that for a dose of IV RhIG ($1,614). In the absence of clearly defined differences in clinical outcomes when treating ITP with IVIG or IV RhIG, the difference in cost may be an important factor in selecting the treatment.

  1. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura.

    PubMed

    García-Méndez, Jorge; Carrillo-Casas, Erika M; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis.

  2. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura.

    PubMed

    García-Méndez, Jorge; Carrillo-Casas, Erika M; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis. PMID:27313917

  3. Cytokine-induced killer cell therapy-associated idiopathic thrombocytopenic purpura: rare but noteworthy.

    PubMed

    Fu, Xiaomin; Zhang, Yong; Gao, Quanli; Lin, Jizhen; Zhang, Qinxian; Xu, Benling; Song, Yongping

    2016-09-01

    Idiopathic thrombocytopenic purpura (ITP) is characterized by a diminished platelet count, an autoimmune condition with antibodies against platelets and an increased tendency to bleed. The association between ITP and solid tumors is uncommon. Cytokine-induced killer (CIK) cell therapy is a well tolerated and promising cancer treatment with minimal toxicity. For the first time, CIK cell therapy was reported to be followed by ITP. The mechanism through which CIK induces ITP remains unclear. Imbalanced ratio of Th cells, decreased numbers or impaired function of Treg cells and excessive secretion of cytokines inducing abnormal activation of B cells may be among the possible reasons. Therefore, a better understanding of this rare condition will require further investigation of these cases. PMID:27485074

  4. Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Kim, Sun Bean; Kim, Do Kyung; Byun, Sun Jeong; Park, Ji Hye; Choi, Jin Young; Park, Young Nyun; Kim, Do Young

    2015-12-01

    Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months. PMID:26770928

  5. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

    SciTech Connect

    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-05-01

    Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

  6. Successful treatment of post thrombotic syndrome with sequential lumbar sympathetic block.

    PubMed

    Gupta, Anita; Portonova, Brittany; Dadachanji, Cyrus

    2015-01-01

    An underappreciated sequelae of deep venous thrombosis (DVT) is the pain associated with the blood clot in the peripheral extremity. Although most frequently acute in nature, DVT occasionally presents with chronic pain in the affected limb. Furthermore, many individuals suffering from prothrombotic states often have recurring pain from DVT. Thus far there has been a paucity in the medical literature in how to treat post thrombotic pain. Post thrombotic syndrome (PTS) can cause a significant decrease in quality of life in individuals who have had a history of a DVT. Symptoms will typically include edema, pain, heaviness of the affected limb, skin changes, ulcers, varicosities, and gait abnormality. An underappreciated approach to treating PTS is the utilization of lumbar sympathetic blocks (LSB). A 68-year-old male who had a history of recurrent right lower extremity deep venous thrombosis presented with complaints of excruciating pain, discomfort, and erythema in his right lower extremity, which was negatively affecting his quality of life and prohibiting him from mobility. The patient attributed his lack of mobility secondary to the thrombotic pain. Compression boot/stocking therapy was not combating the discomfort associated with the PTS, often increasing the severity of the patient's pain. Sequential right lumbar sympathetic blocks were performed, which nearly completely resolved the patient's symptoms and improved the patient's ambulatory status and ability to perform activities of daily living. Sympathetic nerve blocks should be considered as a treatment option for patients who suffer with pain from PTS.

  7. Assessment of the infiltration of inflammatory cells in the walls of thrombotic varicose veins.

    PubMed

    Chu, Hai-bo; Yan, Fei; Zhao, Jian-hua; Xu, Yong-bo; Wang, Tao; Guo, Wen-jun

    2013-01-01

    The purpose of this study is to describe the infiltration of mast cells as well as T and B cells in the walls of thrombotic varicose great saphenous veins. Sections were obtained from venous segments of patients with varicose veins and stained with toluidine blue for mast cells, while immunohistochemistry for T cells (using CD45RO antibody) and B cells (CD20) was analyzed using light microscopy after staining. The number of mast cells, T, and B cells observed in thrombotic varicose veins was 1.925 ± 1.203, 72.038 ± 34.707, and 19.519 ± 9.899, respectively. In varicose veins, the corresponding values were 0.265 ± 0.099, 0.600 ± 0.432, and 0.488 ± 0.400. Significantly higher number of mast cells, T cells, and B cells were observed in thrombotic varicose veins compared with control veins. A significant difference was not observed between the varicose group and control group. Thrombi in varicose veins can induce infiltration of mast cells, T cells, and B cells, which may be involved in the remodeling of venous walls.

  8. Effect of the serotonin antagonist ketanserin on the hemodynamic and morphological consequences of thrombotic infarction

    SciTech Connect

    Dietrich, W.D.; Busto, R.; Ginsberg, M.D. )

    1989-12-01

    The effect of the serotonin (5-hydroxytryptamine, 5-HT) antagonist ketanserin on the remote hemodynamic consequences of thrombotic brain infarction was studied in rats. Treated rats received an injection of 1 mg/kg ketanserin 30 min before and 1 h following photochemically induced cortical infarction. Local CBF (LCBF) was assessed autoradiographically with ({sup 14}C)iodoantipyrine 4 h following infarction, and chronic infarct size was documented at 5 days. Thrombotic infarction led to significant decreases in LCBF within noninfarcted cortical regions. For example, mean LCBF was decreased to 63, 55, and 65% of control (nontreated normal rats) in ipsilateral frontal, lateral, and auditory cortices, respectively. In rats treated with ketanserin, significant decreases in LCBF were not documented within remote cortical areas compared with controls. In contrast to these hemodynamic effects, morphological analysis of chronic infarct size demonstrated no differences in infarct volume between treated (27 +/- 3 mm3) and nontreated (27 +/- 6 mm3) rats. These data are consistent with the hypothesis that 5-HT is involved in the widespread hemodynamic consequences of experimentally induced thrombotic infarction. Remote hemodynamic consequences of acute infarction can be inhibited without altering final infarct size.

  9. Heparin alters viral serpin, serp-1, anti-thrombolytic activity to anti-thrombotic activity.

    PubMed

    Li, Xing; Schneider, Heather; Peters, Andrew; Macaulay, Colin; King, Elaine; Sun, Yunming; Liu, Liying; Dai, Erbin; Davids, Jennifer A; McFadden, Grant; Lucas, Alexandra

    2008-01-01

    Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathways. PMID:18949070

  10. Haematological malignancies in pregnancy: An overview with an emphasis on thrombotic risks.

    PubMed

    Horowitz, Netanel A; Lavi, Noa; Nadir, Yona; Brenner, Benjamin

    2016-09-27

    With increase of maternal age, the incidence of haematological malignancies during pregnancy is rising and posing diagnostic and treatment challenges. Lymphoma is the fourth most common malignancy diagnosed in pregnancy; Hodgkin lymphoma is more frequent in pregnant women than non-Hodgkin lymphoma (NHL). The proportion of highly aggressive lymphomas in pregnant women is significantly higher than in non-pregnant women of reproductive age. Reproductive organ involvement is observed in almost half of pregnant women with NHL. The association of acute leukaemia and pregnancy is infrequent and it is assumed that pregnancy does not accelerate the disease course. Both cancer and pregnancy induce a procoagulant state which can lead to maternal venous thromboembolism (VTE) and placental occlusion. Pregnancy in woman with myeloproliferative neoplasms (MPN) promotes thrombotic environment, associating with an augmented risk of placental thrombosis, intrauterine growth retardation or loss and maternal thrombotic events.Haematological malignancies during pregnancy often require urgent diagnosis and management and are associated with potential adverse fetal outcomes. Most chemotherapeutic agents are teratogenic and should be avoided during the first trimester. Their use during the second and third trimesters may cause intrauterine growth restriction, premature birth and intrauterine fetal death. All chemotherapeutic drugs should be administered only after a detailed discussion with the patient and with close fetal monitoring. Chemotherapy and biological agents might also augment thrombotic risk. Guidelines for VTE prophylaxis in pregnant women with hematologic malignancies, apart from MPN, are currently unavailable, and therefore, clinical judgment should be made in each case. PMID:27465578

  11. Successful treatment of post thrombotic syndrome with sequential lumbar sympathetic block.

    PubMed

    Gupta, Anita; Portonova, Brittany; Dadachanji, Cyrus

    2015-01-01

    An underappreciated sequelae of deep venous thrombosis (DVT) is the pain associated with the blood clot in the peripheral extremity. Although most frequently acute in nature, DVT occasionally presents with chronic pain in the affected limb. Furthermore, many individuals suffering from prothrombotic states often have recurring pain from DVT. Thus far there has been a paucity in the medical literature in how to treat post thrombotic pain. Post thrombotic syndrome (PTS) can cause a significant decrease in quality of life in individuals who have had a history of a DVT. Symptoms will typically include edema, pain, heaviness of the affected limb, skin changes, ulcers, varicosities, and gait abnormality. An underappreciated approach to treating PTS is the utilization of lumbar sympathetic blocks (LSB). A 68-year-old male who had a history of recurrent right lower extremity deep venous thrombosis presented with complaints of excruciating pain, discomfort, and erythema in his right lower extremity, which was negatively affecting his quality of life and prohibiting him from mobility. The patient attributed his lack of mobility secondary to the thrombotic pain. Compression boot/stocking therapy was not combating the discomfort associated with the PTS, often increasing the severity of the patient's pain. Sequential right lumbar sympathetic blocks were performed, which nearly completely resolved the patient's symptoms and improved the patient's ambulatory status and ability to perform activities of daily living. Sympathetic nerve blocks should be considered as a treatment option for patients who suffer with pain from PTS. PMID:25675072

  12. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

    PubMed

    Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul

    2012-07-01

    Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

  13. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. PMID:26186969

  14. Acquired hypofibrinogenemia: current perspectives

    PubMed Central

    Besser, Martin W; MacDonald, Stephen G

    2016-01-01

    Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. PMID:27713652

  15. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach.

  16. Anti-Ku antibody-positive scleroderma-dermatomyositis overlap syndrome developing Graves' disease and immune thrombocytopenic purpura.

    PubMed

    Kamei, Nozomu; Yamane, Kiminori; Yamashita, Yasuyo; Nakanishi, Shuhei; Watanabe, Hiroshi; Fujikawa, Rumi; Hiyama, Keiko; Ishioka, Shinichi; Mendoza, Ciro; Kohno, Nobuoki

    2002-12-01

    Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.

  17. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

    This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…

  18. Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group.

    PubMed

    Go, Ronald S; Winters, Jeffrey L; Leung, Nelson; Murray, David L; Willrich, Maria A; Abraham, Roshini S; Amer, Hatem; Hogan, William J; Marshall, Ariela L; Sethi, Sanjeev; Tran, Cheryl L; Chen, Dong; Pruthi, Rajiv K; Ashrani, Aneel A; Fervenza, Fernando C; Cramer, Carl H; Rodriguez, Vilmarie; Wolanskyj, Alexandra P; Thomé, Stephan D; Hook, C Christopher

    2016-09-01

    Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management. PMID:27497856

  19. Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group.

    PubMed

    Go, Ronald S; Winters, Jeffrey L; Leung, Nelson; Murray, David L; Willrich, Maria A; Abraham, Roshini S; Amer, Hatem; Hogan, William J; Marshall, Ariela L; Sethi, Sanjeev; Tran, Cheryl L; Chen, Dong; Pruthi, Rajiv K; Ashrani, Aneel A; Fervenza, Fernando C; Cramer, Carl H; Rodriguez, Vilmarie; Wolanskyj, Alexandra P; Thomé, Stephan D; Hook, C Christopher

    2016-09-01

    Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management.

  20. Community-acquired pneumonia.

    PubMed

    Prina, Elena; Ranzani, Otavio T; Torres, Antoni

    2015-09-12

    Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.

  1. Systemic Acquired Resistance

    PubMed Central

    2006-01-01

    Upon infection with necrotizing pathogens many plants develop an enhanced resistance to further pathogen attack also in the uninoculated organs. This type of enhanced resistance is referred to as systemic acquired resistance (SAR). In the SAR state, plants are primed (sensitized) to more quickly and more effectively activate defense responses the second time they encounter pathogen attack. Since SAR depends on the ability to access past experience, acquired disease resistance is a paradigm for the existence of a form of “plant memory”. Although the phenomenon has been known since the beginning of the 20th century, major progress in the understanding of SAR was made over the past sixteen years. This review covers the current knowledge of molecular, biochemical and physiological mechanisms that are associated with SAR. PMID:19521483

  2. Clinical significance of determining plasma homocysteine: case-control study on arterial and venous thrombotic patients

    PubMed Central

    Vučković, Biljana A.; Čabarkapa, Velibor S.; Ilić, Tatjana A.; Salatić, Iva R.; Lozanov-Crvenković, Zagorka S.; Mitić, Gorana P.

    2013-01-01

    Aim To determine the differences in plasma homocysteine levels between three MTHFR 677 genotype subgroups in patients with thrombosis and in controls, as well as between patients with thrombosis and controls with the same MTHFR 677 genotype. Methods This case-control study was conducted in Clinical Center of Vojvodina, Novi Sad, from June to December 2011. We included 65 patients with either arterial or venous thrombosis (mean age, 40.97 ± 11.38 years) and 65 controls with no history or clinical evidence of any thrombotic event (mean age, 41.23 ± 11.12 years). Patients and controls were age- and sex-matched. Results In comparison with controls, thrombotic patients had significantly higher homocysteine levels (12.81 ± 4.94 µmol/L vs 9.82 ± 3.68 µmol/L; P < 0.001) and significantly higher incidence of hyperhomocysteinemia (55% vs 22%; P < 0.001; odds ratio [OR] = 4.521). There were no significant differences in homocysteine levels between homozygous carriers, heterozygous carriers, and non-carriers of the MTHFR 677 mutation in either thrombotic patients (12.97 ± 5.40 µmol/L vs 12.55 ± 5.71 µmol/L vs 13.27 ± 1.71 µmol/L; P = 0.100) or controls (10.07 ± 2.50 µmol/L vs 10.25 ± 4.84 µmol/L vs 9.20 ± 2.44 µmol/L; P = 0.651). However, in comparison with controls, homozygous carriers in thrombotic patient group did not have significantly higher levels of homocysteine (12.97 ± 5.40 µmol/L vs 10.07 ± 2.50 µmol/L; P = 0.072), but heterozygous carriers (12.55 ± 5.71 µmol/L vs 10.25 ± 4.84 µmol/L; P = 0.020) and non-carriers (13.27 ± 1.71 µmol/L vs 9.20 ± 2.44 µmol/L; P < 0.001) did. There was no significant difference in homocysteine levels between patients with arterial and venous thrombosis (12.76 ± 3.60 µmol/L vs 12.86 ± 5.51 µmol/L; P = 0.990) and between patients with one thrombotic event and those with recurrent thrombotic events

  3. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    PubMed

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  4. [Thrombotic vasculopathy probably associated with cocaine contaminated with levamisole: report of 2 cases].

    PubMed

    Martínez-Velasco, María Abril; Flores-Suárez, Luis Felipe; Toussaint-Caire, Sonia; Rodríguez-Carreón, Angélica; Díaz-Lozano, Marisol; Sánchez-Armendáriz, Karen

    2015-01-01

    The vasculities are complex diseases. Their cutaneous manifestations are very important and often mirror several pathologies. Cocaine use has been related to both, vasculitis and thrombotic vasculopathy and pseudovasculitis. A new syndrome has been described in association with its adulteration with levamisole. It can be very serious, leading patients to death. This is relevant as levamisole-adultered cocaine seems to be increasingly offered to consumers. Our goal is to report the first two cases in Mexico, which faces an important raise in cocaine use, emphasizing that a high suspicion based on certain characteristics allows for early recognition and adequate treatment.

  5. Acquired methemoglobinemia revisited.

    PubMed

    Trapp, Larry; Will, John

    2010-10-01

    Dentistry has two medications in its pain management armamentarium that may cause the potentially life-threatening disorder methemoglobinemia. The first medications are the topical local anesthetics benzocaine and prilocaine. The second medication is the injectable local anesthetic prilocaine. Acquired methemoglobinemia remains a source of morbidity and mortality in dental and medical patients despite the fact that it is better understood now than it was even a decade ago. It is in the interest of all dental patients that their treating dentists review this disorder. The safety of dental patients mandates professional awareness.

  6. Acquired Multiple Cysts of the Kidney in Neuroblastoma Survivors.

    PubMed

    Moodalbail, Divya G; Apple, Leah Z; Meyers, Kevin E; Ginsberg, Jill P; Kaplan, Bernard S; Bellah, Richard

    2016-07-01

    Cystic kidney disease includes a wide range of hereditary, developmental, and acquired conditions of the kidneys. Some of the inherited causes of cystic kidney disease include autosomal dominant polycystic kidney diseases (caused by mutations in PKD1 or PKD2), autosomal recessive polycystic kidney disease, tuberous sclerosis complex, von Hippel-Lindau disease, oral-facial-digital syndrome type I, and Hadju-Cheney syndrome. Acquired cystic kidney disease has been reported in patients receiving long-term hemodialysis or peritoneal dialysis and in children after liver transplantation. Acute kidney injury can occur in patients with neuroblastoma, usually as a result of thrombotic microangiopathy associated with bone marrow transplantation. End-stage renal disease is described in long-term survivors. However, in this case report, we provide what is to our knowledge the first description of multiple kidney cysts in long-term survivors of stage IV neuroblastoma. None of the 7 patients we describe with neuroblastoma and multiple kidney cysts had a family history of autosomal dominant polycystic kidney disease. Also, all lacked stigmata of tuberous sclerosis complex, von Hippel-Lindau disease, or Hadju-Cheney syndrome. Two patients progressed to end-stage renal disease; in addition, one of them developed an oncocytoid renal cell carcinoma. PMID:27016049

  7. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    PubMed Central

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10–15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×109/L) or partial (platelet count between 50 and 150×109/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients. PMID:21589818

  8. [Clinical significance of Helicobacter pylori in children with idiopathic thrombocytopenic purpura].

    PubMed

    Tang, Ying; Wang, Shu-Chun; Wang, Lu-Juan; Liu, Yong; Wang, Hai-Ying; Wang, Zhan-Ju

    2013-04-01

    This study was aimed to investigate the clinic significance of helicobacter pylori (HP) in children with idiopathic thrombocytopenic purpura (ITP). The infection of HP in 92 ITP children was determined by (13) C-Urea Breath Test, the same test was also performed on 66 healthy children. The 68 children infected with HP were randomly divided into 2 groups: single drug group treated only with corticosteroid and; combined drug group treated with corticosteroid and anti-helicobacter pylori treatment. The results showed that 68 patients infected with HP were found in 92 ITP children (74.7%), 26 patients infected with HP were observed in 66 healthy children (39.4%), which was lower than that in ITP children (74.7%, P < 0.05). After anti-helicobacter pylori therapy, the total effective rate and cure rate of ITP patients increased respectively from 73.5% to 94.1%, and the total recurrence rate (17.0%) was much lower than single drug group (47.1%, P < 0.05). Otherwise, after therapy the platelet count in both two groups increased continuously, and at the same time point, the platelet count in anti-helicobacter pylori group was higher than that in the single drug group (P < 0.05). It is concluded that the ITP children have a higher infection rate of HP, which may be involved in the pathogenesis of ITP. Anti-helicobacter pylori therapy would help to improve the therapeutic efficacy and reduce the recurrence of ITP children.

  9. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

    2008-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

  10. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines.

    PubMed

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy.

  11. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    PubMed Central

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

  12. Renal failure after anti-D globulin treatment of idiopathic thrombocytopenic purpura.

    PubMed

    Kees-Folts, Deborah; Abt, Arthur B; Domen, Ronald E; Freiberg, Andrew S

    2002-02-01

    Idiopathic thrombocytopenic purpura (ITP) is a disorder of rapid destruction of antibody-coated platelets. Anti-D immune globulin has been used for treatment of ITP in the United States since 1995. Initial studies identified no significant side effects of treatment. However, a recent report highlighted occasional episodes of intravascular hemolysis after anti-D immune globulin. We describe two children with ITP who developed acute renal failure (ARF) after treatment with anti-D immune globulin and also analyze ten additional cases of ARF reported to the manufacturer, Cangene Corporation, through postmarketing surveillance. All episodes of ARF were associated with intravascular hemolysis. Four patients required dialysis. Patient age ranged from 1 to 82 years, but those requiring dialysis were all under age 15 years. Several patients with ARF had preexisting creatinine elevation. Three of the patients with ARF had serologic evidence of acute Epstein-Barr virus (EBV) infection. Renal biopsy in one patient showed acute tubular necrosis, with findings consistent with pigment nephropathy. Anti-D immune globulin, used to treat ITP, may be associated with intravascular hemolysis and resultant ARF. Renal function should be monitored in patients with evidence of intravascular hemolysis. Children and adolescents may have increased risk of ARF requiring dialysis.

  13. Vaccine administration and the development of immune thrombocytopenic purpura in children.

    PubMed

    Cecinati, Valerio; Principi, Nicola; Brescia, Letizia; Giordano, Paola; Esposito, Susanna

    2013-05-01

    The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community. PMID:23324619

  14. Importance of immature platelet fraction as predictor of immune thrombocytopenic purpura

    PubMed Central

    Naz, Arshi; Mukry, Samina Naz; Shaikh, Mahwish Rauf; Bukhari, Ali Raza; Shamsi, Tahir Sultan

    2016-01-01

    Background and Objective: Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura) or extravasation of blood from capillaries into skin and mucous membranes (petechiae). The diagnosis of ITP can be made clinically on the basis of symptoms, we need to see if ITP can be confirmed in patients by quantification of residual RNA containing immature platelets (megakaryocytic mass) or immature platelets fraction (IPF) using automated hematology analyzers (Sysmex XE-2100). Methods: In order to check the efficacy of IPF% parameter of Sysmex XE-2100 a total of 231 patients of thrombocytopenia were included in this study. Complete blood count (CBC) was estimated. The data was statistically analyzed by SPSS version 17. Results: About 62 patients were diagnosed as ITP and 169 patients were diagnosed as non ITP on the basis of clinical history. The mean IPF % value of ITP patients was 16.39% and the IPF % value of Non ITP patients was ~7.69% respectively. There was no significant difference in IPF% values with respect to time between sampling and acquisition of complete blood count. The diagnostic sensitivity of IPF% as biomarker for ITP and non-ITP was 85.71% (95%CI: 84.04% to 85.96%) and 41.76% (95% CI: 39.87% to 43.65%). Conclusion: The mean IPF % value by Sysmex XE-2100 can be used to predict ITP. PMID:27375692

  15. Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura

    PubMed Central

    Komoğlu, Sabiha; Silte, Duygu; Sertbaş, Meltem; Sertbaş, Yaşar; Özdemir, Ali

    2015-01-01

    The association of rheumatoid arthritis (RA) and immune thrombocytopenic purpura (ITP) has been reported rarely. Methotrexate, which is used for RA treatment, causes thrombocytopenia. Therefore, in medical practice, physicians avoid using methotrexate for RA in patients who have both RA and ITP. Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy. A 50-year-old woman was diagnosed with diabetes mellitus in 1990, RA in 1995, and ITP in 2000. She had received hydroxychloroquine for more than 5 years. She was treated with prednisolone 16 mg/daily between 2006 and 2007, but she discontinued this therapy because of weight gain. Laboratory findings were not remarkable, except for thrombocytopenia. We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse. The methotrexate dose was increased up to 15 mg/week. Her complete blood cell count was monitored frequently. We did not observe any decrease in platelet count, while active arthritis symptoms of the patient were relieved. This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring.

  16. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    SciTech Connect

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E. )

    1989-09-01

    Splenic dynamics of {sup 111}In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of {sup 111}In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 {plus minus} 0.7 min vs. 3.6 {plus minus} 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 {plus minus} 5 min vs. 13.2 {plus minus} 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

  17. Platelet antibodies of the IgM class in immune thrombocytopenic purpura

    SciTech Connect

    Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.

    1985-04-01

    The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

  18. Platelet Kinetics in Idiopathic Thrombocytopenic Purpura Patients Treated with Thrombopoietin Receptor Agonists

    PubMed Central

    Meyer, Oliver; Herzig, Eric; Salama, Abdulgabar

    2012-01-01

    Aim Thrombopoietin receptor agonists (Tpo RA) increase platelet counts in the majority of chronic autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) patients. It is unknown whether this treatment may also improve platelet survival (PS) in these patients. Methods In order to determine platelet survival (PS), autologous platelets were labeled with 111In oxine and retransfused in six patients under treatment with Tpo RA (romiplostim n = 3; eltrombopag n = 3). Results Stable platelet counts of greater than 100 × 103/μl were observed in all 6 patients. Platelet survival was decreased in all cases (mean 2.10 days; range 0.13–3.73 days). No correlation was found between platelet count and PS. Similarly, there was no significant relationship between platelet turnover and platelet count. However, a high platelet turnover, exceeding 25 or three times the norm was observed in 2 patients who presented the lowest PS (0.13 or 0.83 days). Two patients had a moderately shortened PS (1.91 or 2.42 days), and, correspondingly, a moderately increased platelet turnover rate (63,072 or 72,872 platelets/μl/day). Conclusion These results indicate that Tpo RA may not only overcompensate platelet destruction in ITP, but may interfere with other mechanisms, which, in some cases, results in a reduced platelet destruction rate. PMID:22896760

  19. Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer.

    PubMed

    Teoh, Jeremy Yc; Chan, Samson Ys; Chiu, Peter Kf; Poon, Darren Mc; Cheung, Ho-Yuen; Hou, Simon Sm; Ng, Chi-Fai

    2015-01-01

    We investigated the cardiovascular thrombotic risk after surgical castration (SC) versus gonadotropin-releasing hormone agonists (GnRHa) in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3 ± 7.5 years) was significantly higher than the GnRHa group (71.8 ± 8.3 years) (P < 0.001). There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis (P = 0.014). Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P< 0.001), hyperlipidemia (HR 2.455, 95% CI 1.53-3.93, P< 0.001), and SC (HR 1.648, 95% CI 1.05-2.59, P= 0.031) were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

  20. A COL4A5 mutation with glomerular disease and signs of chronic thrombotic microangiopathy.

    PubMed

    Wuttke, Matthias; Seidl, Maximilian; Malinoc, Angelica; Prischl, Friedrich C; Kuehn, E Wolfgang; Walz, Gerd; Köttgen, Anna

    2015-12-01

    COL4A5 mutations are a known cause of Alport syndrome, which typically manifests with haematuria, hearing loss and ocular symptoms. Here we report on a 16-year-old male patient with a negative family history who presented with proteinuria, progressive renal failure and haemolysis, but without overt haematuria or hearing loss. A renal biopsy revealed features of atypical IgA nephropathy, while a second biopsy a year later showed features of focal segmental glomerulosclerosis, but was finally diagnosed as chronic thrombotic microangiopathy. Targeted sequencing of candidate genes for steroid-resistant nephrotic syndrome and congenital thrombotic microangiopathy was negative. Despite all therapeutic efforts, including angiotensin-converting enzyme inhibition, immunosuppressive therapy, plasma exchanges and rituximab, the patient progressed to end-stage renal disease. When a male cousin presented with nephrotic syndrome years later, whole-exome sequencing identified a shared disruptive COL4A5 mutation (p.F222C) that showed X-linked segregation. Thus, mutations in COL4A5 give rise to a broader spectrum of clinical presentation than commonly suspected, highlighting the benefits of comprehensive rather than candidate genetic testing in young patients with otherwise unexplained glomerular disease. Our results are in line with an increasing number of atypical presentations of single-gene disorders identified through genome-wide sequencing.

  1. Fibrin structure in organized thrombotic material removed during pulmonary artery endarterectormy: the effect of vessel calibre.

    PubMed

    Mazur, Piotr; Gawęda, Bogusław; Natorska, Joanna; Ząbczyk, Michał; Undas, Anetta; Sadowski, Jerzy; Kopeć, Grzegorz; Waligóra, Marcin; Podolec, Piotr; Kapelak, Bogusław

    2016-08-01

    Pulmonary endarterectomy (PEA) is a curative therapeutic approach in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The location-dependent structural differences of thrombotic material found in pulmonary arteries in CTEPH are poorly investigated. We present the case of a 47-year-old woman with antiphospholipid syndrome, diabetes mellitus and abnormal fibrin phenotype, who underwent PEA for CTEPH. Intravascular material removed bilaterally during PEA (from lobar, segmental and sub-segmental arteries) has been studied using light and scanning electron microscopy (SEM). Light microscopy showed tighter fibrous network in the portions of intraluminal thrombotic material facing the vessel wall, which contained collagen and fibrin fibers, and abundant cells. Cells, evaluated by immunostaining, were present in the whole removed material. Tissue factor expression was also observed with the highest values in the portions of intravascular material facing the vessel wall. In the main pulmonary arteries, SEM images revealed thick fibers of fibrous proteins loosly meshed and few erythrocytes and platelets between them (both dysmorphic "wedged" and fresh cells were present). In the fibrotic layers, containing mainly collagen and fibrin, removed from the lobar/segmental pulmonary arteries we found a stepwise increase in fiber density with decreasing vessel calibre, followed by denser fibrous networks composed of thinner fibers. Elastic fibers in the lobar and segmental arteries were aligned along the blood flow vector. These findings demonstrate differences in the structure of endarterectomized PEA material dependent on the vessel calibre and might contribute to understanding of CTEPH pathophysiology.

  2. Anti-thrombotic effect of rutin isolated from Dendropanax morbifera Leveille.

    PubMed

    Choi, Jun-Hui; Kim, Dae-Won; Park, Se-Eun; Lee, Hyo-Jeong; Kim, Ki-Man; Kim, Kyung-Je; Kim, Myung-Kon; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases. PMID:25777266

  3. CFD-based Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

    NASA Astrophysics Data System (ADS)

    Sengupta, Dibyendu; Kung, Ethan; Kahn, Andrew; Burns, Jane; Marsden, Alison

    2012-11-01

    Coronary aneurysms occur in 25% of untreated Kawasaki Disease (KD) patients and put patients at increased risk for myocardial infarction and sudden death. Clinical guidelines recommend using aneurysm diameter >8 mm as the arbitrary criterion for treating with anti-coagulation therapy. This study uses patient-specific modeling to non-invasively determine hemodynamic parameters and quantify thrombotic risk. Anatomic models were constructed from CT angiographic image data from 5 KD aneurysm patients and one normal control. CFD simulations were performed to obtain hemodynamic data including WSS and particle residence times (PRT). Thrombosis was clinically observed in 4/9 aneurysmal coronaries. Thrombosed vessels required twice as many cardiac cycles (mean 8.2 vs. 4.2) for particles to exit, and had lower mean WSS (1.3 compared to 2.8 dynes/cm2) compared to vessels with non-thrombosed aneurysms of similar max diameter. 1 KD patient in the cohort with acute thrombosis had diameter < 8 mm. Regions of low WSS and high PRT predicted by simulations correlated with regions of subsequent thrombus formation. Thrombotic risk stratification for KD aneurysms may be improved by incorporating both hemodynamic and geometric quantities. Current clinical guidelines to assess patient risk based only on aneurysm diameter may be misleading. Further prospective study is warranted to evaluate the utility of patient-specific modeling in risk stratifying KD patients with coronary aneurysms. NIH R21.

  4. Transluminal Attenuation Gradient for Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

    NASA Astrophysics Data System (ADS)

    Grande Gutierrez, Noelia; Kahn, Andrew; Burns, Jane; Marsden, Alison

    2014-11-01

    Kawasaki Disease (KD) can result in coronary aneurysms in up to 25% of patients if not treated early putting patients at risk of thrombus formation, myocardial infarction and sudden death. Clinical guidelines for administering anti-coagulation therapy currently rely on anatomy alone. Previous studies including patient specific modeling and computer simulations in KD patients have suggested that hemodynamic data can predict regions susceptible to thrombus formation. In particular, high Particle Residence Time gradient (PRTg) regions have shown to correlate with regions of thrombus formation. Transluminal Attenuation Gradient (TAG) is determined from the change in radiological attenuation per vessel length. TAG has been used for characterizing coronary artery stenoses, however this approach has not yet been used in aneurysmal vessels. The aim of this study is to analyze the correlation between TAG and PRTg in KD patients with aneurysms and evaluate the use of TAG as an index to quantify thrombotic risk. Patient specific anatomic models for fluids simulations were constructed from CT angiographic image data from 3 KD aneurysm patients and one normal control. TAG values for the aneurysm patients were markedly lower than for the non-aneurysmal patient (mean -18.38 vs. -2). In addition, TAG values were compared to PRTg obtained for each patient. Thrombotic risk stratification for KD aneurysms may be improved by incorporating TAG and should be evaluated in future prospective studies.

  5. A COL4A5 mutation with glomerular disease and signs of chronic thrombotic microangiopathy

    PubMed Central

    Wuttke, Matthias; Seidl, Maximilian; Malinoc, Angelica; Prischl, Friedrich C.; Kuehn, E. Wolfgang; Walz, Gerd; Köttgen, Anna

    2015-01-01

    COL4A5 mutations are a known cause of Alport syndrome, which typically manifests with haematuria, hearing loss and ocular symptoms. Here we report on a 16-year-old male patient with a negative family history who presented with proteinuria, progressive renal failure and haemolysis, but without overt haematuria or hearing loss. A renal biopsy revealed features of atypical IgA nephropathy, while a second biopsy a year later showed features of focal segmental glomerulosclerosis, but was finally diagnosed as chronic thrombotic microangiopathy. Targeted sequencing of candidate genes for steroid-resistant nephrotic syndrome and congenital thrombotic microangiopathy was negative. Despite all therapeutic efforts, including angiotensin-converting enzyme inhibition, immunosuppressive therapy, plasma exchanges and rituximab, the patient progressed to end-stage renal disease. When a male cousin presented with nephrotic syndrome years later, whole-exome sequencing identified a shared disruptive COL4A5 mutation (p.F222C) that showed X-linked segregation. Thus, mutations in COL4A5 give rise to a broader spectrum of clinical presentation than commonly suspected, highlighting the benefits of comprehensive rather than candidate genetic testing in young patients with otherwise unexplained glomerular disease. Our results are in line with an increasing number of atypical presentations of single-gene disorders identified through genome-wide sequencing. PMID:26613025

  6. [A case of pulmonary tumor thrombotic microangiopathy induced by early gastric cancer].

    PubMed

    Yasui, Hideki; Akamatsu, Taisuke; Nakamura, Yutarou; Inui, Naoki; Suda, Takafumi; Chida, Kingo; Meguro, Shiori; Baba, Satoshi

    2011-02-01

    A 56-year-old man with chief complaints of dry cough and dyspnea was admitted. He had severe hypoxemia, and his chest radiographs showed enhancement of pulmonary artery opacities with multiple defects on pulmonary blood flow scintigraphy. Enhanced computed tomography (CT) revealed swelling of the mediastinum and hilar lymph nodes, but no apparent thrombi in the pulmonary arteries was seen. A biopsy specimen of a left neck lymph node showed poorly differentiated adenocarcinoma, including signet-ring cell carcinoma components, but the origin was unclear. Despite receiving chemotherapy, his respiratory condition worsened, and he died 3 days after admission. Routine autopsy failed to clarify the tumor origin, but a detailed dissection of specimens confirmed early gastric cancer. Additionally, pathology of the pulmonary arteries was compatible with pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Accompanied with early gastric cancer, this is an extremely rare but important case of PTTM. PMID:21400909

  7. [Successful treatment of allergic purpura nephritis associated with thrombotic microangiopathy using plasma exchange: a case report].

    PubMed

    Kuwabara, Takashige; Ohnishi, Takahiro; Kakuta, Yutaka; Nomura, Shinsuke; Joh, Kensuke

    2004-01-01

    A 73-year-old man, who had an allergy to shellfish, was admitted to our hospital because of proteinuria, hematuria, purpura and extremity edema after eating oysters. Laboratory data on admission were proteinuria 2.0 g/day, hematuria 3+, serum creatinine (Cr) 1.2 mg/dl, total protein 6.3 g/dl, and albumin 3.1 g/dl. He presented a high fever with neutrophilia and rapid deterioration of renal function after admission. Based on the skin biopsy, we made a diagnosis of leukocytoclastic vasculitis with IgA deposition. Oral prednisolone (40 mg/day) following drip intravenous methylprednisolone (500 mg/day, 3 days) was administered. However, renal function and urinary findings showed no sign of improvement. In the first renal biopsy, although there were no crescentic formations, most of the glomeruli showed thrombotic microangiopathy and endocapillary proliferation with IgA deposition and electron dense deposits. Therefore, a plasma exchange was performed resulting in an improvement of the renal function. The serum Cr. level was reduced from 2.7 to 0.8 mg/dl and proteinuria from 3.7 to 0.1 g/day. In the second biopsy, the electron dense deposits with an IgA deposition had disappeared. These findings suggested that plasma exchange was effective in leading remission in a case of allergic purpura nephritis associated with thrombotic microangiopathy.

  8. A Case Report: Cavitary Infarction Caused by Pulmonary Tumor Thrombotic Microangiopathy in a Patient with Pancreatic Intraductal Papillary Mucinous Neoplasm.

    PubMed

    Bae, Kyoungkyg; Kwon, Woon-Jung; Choi, Seong Hoon; Lee, Jong Hwa; Cha, Hee Jeong

    2015-01-01

    Pulmonary tumor embolism is commonly discovered at autopsy, but is rarely suspected ante-mortem. Microangiopathy is an uncommon and distinct form of simple tumor pulmonary embolism. Here, we present a 52-year-old male with tumor thrombotic microangiopathy and pulmonary infarction, which might have originated from intraductal papillary mucinous tumor of the pancreas. Multiple wedge-shaped consolidations were found initially and aggravated with cavitation. These CT features of pulmonary infarction were pathologically confirmed to result from pulmonary tumor thrombotic microangiopathy. PMID:26175596

  9. Community-acquired pneumonia.

    PubMed

    Polverino, E; Torres Marti, A

    2011-02-01

    Despite the remarkable advances in antibiotic therapies, diagnostic tools, prevention campaigns and intensive care, community-acquired pneumonia (CAP) is still among the primary causes of death worldwide, and there have been no significant changes in mortality in the last decades. The clinical and economic burden of CAP makes it a major public health problem, particularly for children and the elderly. This issue provides a clinical overview of CAP, focusing on epidemiology, economic burden, diagnosis, risk stratification, treatment, clinical management, and prevention. Particular attention is given to some aspects related to the clinical management of CAP, such as the microbial etiology and the available tools to achieve it, the usefulness of new and old biomarkers, and antimicrobial and other non-antibiotic adjunctive therapies. Possible scenarios in which pneumonia does not respond to treatment are also analyzed to improve clinical outcomes of CAP. PMID:21242952

  10. Acquired storage pool deficiency with increased platelet-associated IgG. Report of five cases.

    PubMed

    Weiss, H J; Rosove, M H; Lages, B A; Kaplan, K L

    1980-11-01

    Acquired abnormalities of platelet aggregation have been reported with increasing frequency. We studied five patients (including two with systemic lupus erythematosus and one with compensated chronic idiopathic thrombocytopenic purpura) in whom platelet aggregation responses to collagen, epinephrine and ADP are impaired; in all cases, we found that levels of platelet-associated immunoglobulin G (IgG) were increased. In all five patients substances stored in platelet-dense granules (ATP, ADP, serotonin and calcium) were diminished. The content of the alpha-granule substance, beta-thromboglobulin, was also decreased in most cases, whereas the levels of two secretable acid hydrolase enzymes (beta-glucuronidase and beta-N-acetyl glucosaminidase) were within normal limits. These findings are similar to those observed in subtypes of congenital storage pool deficiency. However, in contrast to the congenital disorder, a membrane-bound (nonsecretable) acid phosphatase was also decreased in the patients with acquired storage pool deficiency. These findings suggest that impaired platelet aggregation on an acquired basis may, in some patients, be due to immune platelet damage resulting in a distinctive type of platelet storage pool deficiency. PMID:6449150

  11. Balancing Therapy with Thrombopoietin Receptor Agonists and Splenectomy in Refractory Immune Thrombocytopenic Purpura: A Case of Postsplenectomy Thrombocytosis Requiring Plateletpheresis

    PubMed Central

    Zimmerman, Jacquelyn; Norsworthy, Kelly J.

    2016-01-01

    Immune thrombocytopenic purpura (ITP) causes thrombocytopenia through the autoimmune destruction of platelets. Corticosteroids remain the first line of therapy, and traditionally splenectomy has been the second. While the availability of thrombopoietin receptor agonists (TPO-RAs) has expanded treatment options, there is little data for the ideal management of these agents in preparation for splenectomy. Thrombocytosis has been reported after splenectomy in patients treated with TPO-RA preoperatively, with one prior case requiring plateletpheresis for symptomatic thrombocytosis. We present a case report and review of the literature pertaining to this complication and provide recommendations for preventing postsplenectomy thrombocytosis in ITP patients on TPO-RAs. PMID:27812394

  12. Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature.

    PubMed

    Huenerberg, Katherine; Hudspeth, Michelle; Bergmann, Shayla; Pai, Shashidhar; Singh, Balvir; Duong, Angie

    2016-05-01

    Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients. PMID:26854214

  13. Acquired aplastic anemia.

    PubMed

    Keohane, Elaine M

    2004-01-01

    Acquired aplastic anemia (AA) is a disorder characterized by a profound deficit of hematopoietic stem and progenitor cells, bone marrow hypocellularity, and peripheral blood pancytopenia. It primarily affects children, young adults, and those over 60 years of age. The majority of cases are idiopathic; however, idiosyncratic reactions to some drugs, chemicals, and viruses have been implicated in its etiology. An autoimmune T-cell reaction likely causes the stem cell depletion, but the precise mechanism, as well as the eliciting and target antigens, is unknown. Symptoms vary from severe life-threatening cytopenias to moderate or non-severe disease that does not require transfusion support. The peripheral blood typically exhibits pancytopenia, reticulocytopenia, and normocytic or macrocytic erythrocytes. The bone marrow is hypocellular and may exhibit dysplasia of the erythrocyte precursors. First line treatment for severe AA consists of hematopoietic stem cell transplantation in young patients with HLA identical siblings, while immunosuppression therapy is used for older patients and for those of any age who lack a HLA matched donor. Patients with AA have an increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute leukemia. Further elucidation of the pathophysiology of this disease will result in a better understanding of the interrelationship among AA, PNH, and MDS, and may lead to novel targeted therapies.

  14. Changes in Follicular Helper T Cells in Idiopathic Thrombocytopenic Purpura Patients

    PubMed Central

    Xie, Jue; Cui, Dawei; Liu, Yan; Jin, Jie; Tong, Hongyan; Wang, Lei; Ruan, Guoxiang; Lu, Yun; Yuan, Huiming

    2015-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP. Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR. Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients. Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients. PMID:25561904

  15. Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura.

    PubMed

    Satoh, Takashi; Pandey, Janardan P; Okazaki, Yuka; Yasuoka, Hidekata; Kawakami, Yutaka; Ikeda, Yasuo; Kuwana, Masataka

    2004-03-01

    Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)-alpha (-238 G/A and -308 G/A), TNF-beta (+252 G/A), and interleukin (IL)-1beta (-511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF-beta (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0.04, odds ratio = 3.6, 95% confidence interval 1.1-11.1), while no significant association was detected for the other SNPs. The distribution of the TNF-beta (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the TNF-beta (+252) G/G phenotype than in those with the G/A or A/A phenotype (11.9 +/- 4.9 vs. 6.8 +/- 4.9 and 3.7 +/- 2.8 per 10(5) peripheral blood mononuclear cells; P = 0.02 and P < 0.001, respectively). These findings suggest that the SNP located at TNF-beta (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins.

  16. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography

    PubMed Central

    Frydman, Galit H.; Davis, Nick; Beck, Paul L.; Fox, James G.

    2015-01-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state. PMID:25728540

  17. Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.

    PubMed

    Perricone, Carlo; Ceccarelli, Fulvia; Nesher, Gideon; Borella, Elisabetta; Odeh, Qasim; Conti, Fabrizio; Shoenfeld, Yehuda; Valesini, Guido

    2014-12-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.

  18. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state. PMID:25728540

  19. CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura.

    PubMed

    Xu, Jiannan; Zhao, Liyun; Zhang, Yan; Guo, Qingxu; Chen, Hui

    2016-01-01

    BACKGROUND Epidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP). MATERIAL AND METHODS Published studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results. RESULTS In total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all P<0.05). However, no similar associations were found between CD32 131H>R polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05). CONCLUSIONS Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP. PMID:27315784

  20. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.

  1. Pulmonary tumor thrombotic microangiopathy associated with urothelial carcinoma of the urinary bladder: antemortem diagnosis by pulmonary microvascular cytology.

    PubMed

    Yamakawa, Hideaki; Yoshida, Masahiro; Yamada, Masami; Ishikawa, Takeo; Takagi, Masamichi; Katagi, Hiroaki; Yoshida, Jun; Kosuga, Tsuneharu; Kuwano, Kazuyoshi

    2015-09-01

    PTTM (Pulmonary tumor thrombotic microangiopathy) is very difficult to diagnose before death. We report a case of urothelial carcinoma of the urinary bladder associated with PTTM in which an antemortem diagnosis by PMC (pulmonary microvascular cytology). PMC may represent the only chance for diagnosis and achievement of remission in PTTM. PMID:26401277

  2. Adjunctive therapies to reduce thrombotic events in patients with a history of myocardial infarction: role of vorapaxar.

    PubMed

    Farag, Mohamed; Patel, Hiten; Gorog, Diana A

    2015-01-01

    Acute myocardial infarction (AMI) is generally attributed to coronary atherothrombotic disease. Platelet activation is essential for thrombus formation and is thus an important target for pharmacological intervention to prevent and treat AMI. Despite contemporary treatment with dual antiplatelet therapy, including acetylsalicylic acid and adenosine diphosphate receptor antagonists, patients with prior AMI remain at increased risk of future thrombotic events. This has stimulated the search for more potent antithrombotic agents. Among these is the oral protease-activated receptor-1 antagonist vorapaxar, which represents a new oral antiplatelet agent to reduce thrombotic risk in patients with atherothrombotic disease. The TRACER and the TRA 2°P-TIMI 50 trials concluded that vorapaxar in addition to standard therapy reduced ischemic adverse cardiac events. A remarkable benefit was observed in patients with stable atherosclerotic disease, particularly those with a previous history of AMI. Although favorable effects were seen in reduction of adverse cardiac events, this was associated with excess major and intracranial bleeding, particularly in patients at high risk of bleeding and those with a history of stroke or transient ischemic attack. Currently, the lack of a reliable individualized risk stratification tool to assess patients for thrombotic and bleeding tendencies in order to identify those who might gain most net clinical benefit has led to limited use of vorapaxar in clinical practice. Vorapaxar may find a niche as an adjunct to standard care in patients at high risk of thrombotic events and who are at low risk of bleeding. PMID:26229441

  3. Thrombotic microangiopathy: expanding genetic, clinical and therapeutic spectra and the need for worldwide implementation of recent advances.

    PubMed

    Sanchez-Niño, Maria D; Ortiz, Alberto

    2015-12-01

    In this issue of CKJ, four reports address different aspects of a rare condition, thrombotic microangiopathy, including atypical haemolytic uraemic syndrome. For rare diseases, a single case report may provide hypothesis-generating information that may lead to concept-changing research with the potential to influence patient care. The present reports and small series illustrate the following aspects of thrombotic microangiopathy: (i) the role of whole-exome sequencing and of repeating the family history assessment over time in reducing the number of chronic kidney disease patients with non-specific diagnosis (e.g. focal segmental glomerulosclerosis without any further indication as to aetiology or hypertension-attributed kidney disease) and the need for further studies on the potential for type IV collagen mutations to be associated with thrombotic microangiopathy, i.e. the potential for an expanding genetic spectrum; (ii) the expanding clinical spectrum from an acute catastrophic disease to a chronic, mild, stable condition with unknown long-term consequences and uncharted therapeutic approaches; (iii) the expanding therapeutic spectrum, with the successful use of eculizumab to treat thrombotic microangiopathy in the context of overlap autoimmune disease and (iv) the huge worldwide inequalities in the implementation of these and other advances. International collaboration is needed to address these issues and should encompass the wider use of already available registries for this rare disease and the worldwide implementation of current effective, yet expensive, therapies. PMID:26613024

  4. Thrombotic microangiopathy: expanding genetic, clinical and therapeutic spectra and the need for worldwide implementation of recent advances

    PubMed Central

    Sanchez-Niño, Maria D.; Ortiz, Alberto

    2015-01-01

    In this issue of CKJ, four reports address different aspects of a rare condition, thrombotic microangiopathy, including atypical haemolytic uraemic syndrome. For rare diseases, a single case report may provide hypothesis-generating information that may lead to concept-changing research with the potential to influence patient care. The present reports and small series illustrate the following aspects of thrombotic microangiopathy: (i) the role of whole-exome sequencing and of repeating the family history assessment over time in reducing the number of chronic kidney disease patients with non-specific diagnosis (e.g. focal segmental glomerulosclerosis without any further indication as to aetiology or hypertension-attributed kidney disease) and the need for further studies on the potential for type IV collagen mutations to be associated with thrombotic microangiopathy, i.e. the potential for an expanding genetic spectrum; (ii) the expanding clinical spectrum from an acute catastrophic disease to a chronic, mild, stable condition with unknown long-term consequences and uncharted therapeutic approaches; (iii) the expanding therapeutic spectrum, with the successful use of eculizumab to treat thrombotic microangiopathy in the context of overlap autoimmune disease and (iv) the huge worldwide inequalities in the implementation of these and other advances. International collaboration is needed to address these issues and should encompass the wider use of already available registries for this rare disease and the worldwide implementation of current effective, yet expensive, therapies. PMID:26613024

  5. Eculizumab Treatment in a Patient with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy and Steroid-Refractory Acute Graft Versus Host Disease.

    PubMed

    Fernández, Cristina; Lario, Ana; Forés, Rafael; Cabrera, Rafael

    2015-11-23

    A 30-year-old man with acquired aplastic anemia underwent an HLA-identical bone marrow transplant. He developed a grade III acute graft versus host disease (GVHD) refractory to various lines of treatment. On post-transplant day 196, he was diagnosed with stem cell transplantation-associated thrombotic micro-angiopathy (HSCT-TMA) and he received treatment with eculizumab 900 mg iv weekly for 4 doses followed by a single dose of 1200 mg 2 weeks later. After the first dose of eculizumab, the patient ceased to require transfusions and a progressive improvement in analytical parameters for microangiopathy was observed until their complete normalization. Coinciding with the improved of HSCT-TMA, the patient presented a clear response to his acute GVHD with disappearance of the diarrhea and bilirubin normalization. He was discharged eight weeks after the start of treatment. Unfortunately, one month later, the patient was readmitted for a GVHD relapse and he died two weeks later by an acute respiratory distress syndrome. In our case, the rapid clinical and analytical response to early treatment with eculizumab supports the implication of the complement in HSCT-TMA and suggests that the drug has a beneficial effect when used as coadjuvant therapy in acute GVHD.

  6. Nonbacterial Thrombotic Endocarditis with Recurrent Embolic Events as Manifestation of Ovarian Neoplasm

    PubMed Central

    Aryana, Arash; Esterbrooks, Dennis J; Morris, Peter C

    2006-01-01

    We describe the case of a 43-year-old woman with transient ischemic neurologic deficits and recurrent systemic and pulmonary emboli in whom infectious work-up and extensive thrombophilic evaluation were unremarkable. Transesophageal echocardiography (TEE) established the diagnosis of nonbacterial thrombotic endocarditis (NBTE). This is a rare condition often associated with hypercoagulable states or advanced malignancy such as adenocarcinomas, characterized by cardiac vegetations along valvular coaptation lines without destruction of leaflets. In our patient, we diagnosed an ovarian clear cell adenocarcinoma, a malignant disorder that has been rarely reported in association with NBTE. This case illustrates that NBTE can present as an atypical manifestation of malignancy and must be distinguished from infective endocarditis, which implies a different therapeutic strategy. When confronted with findings of NBTE without a clear etiology, an occult neoplasm must be excluded. Anticoagulant therapy is the mainstay of treatment. However, cardiac vegetations may require surgical intervention in rare instances. PMID:16965557

  7. Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel.

    PubMed

    Vedantham, Suresh; Kahn, Susan R; Goldhaber, Samuel Z; Comerota, Anthony J; Parpia, Sameer; Meleth, Sreelatha; Earp, Diane; Williams, Rick; Sista, Akhilesh K; Marston, William; Rathbun, Suman; Magnuson, Elizabeth A; Razavi, Mahmood K; Jaff, Michael R; Kearon, Clive

    2016-08-01

    Patients with advanced post-thrombotic syndrome (PTS) and chronic iliac vein obstruction suffer major physical limitations and impairment of health-related quality of life. Currently there is a lack of evidence-based treatment options for these patients. Early studies suggest that imaging-guided, catheter-based endovascular therapy can eliminate iliac vein obstruction and saphenous venous valvular reflux, resulting in reduced PTS severity; however, these observations have not been rigorously validated. A multidisciplinary expert panel meeting was convened to plan a multicenter randomized controlled clinical trial to evaluate endovascular therapy for the treatment of advanced PTS. This article summarizes the findings of the panel, and is expected to assist in developing a National Institutes of Health-sponsored clinical trial and other studies to improve the care of patients with advanced PTS.

  8. Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel

    PubMed Central

    Vedantham, Suresh; Kahn, Susan R; Goldhaber, Samuel Z; Comerota, Anthony J; Parpia, Sameer; Meleth, Sreelatha; Earp, Diane; Williams, Rick; Sista, Akhilesh K; Marston, William; Rathbun, Suman; Magnuson, Elizabeth A; Razavi, Mahmood K; Jaff, Michael R; Kearon, Clive

    2016-01-01

    Patients with advanced post-thrombotic syndrome (PTS) and chronic iliac vein obstruction suffer major physical limitations and impairment of health-related quality of life. Currently there is a lack of evidence-based treatment options for these patients. Early studies suggest that imaging-guided, catheter-based endovascular therapy can eliminate iliac vein obstruction and saphenous venous valvular reflux, resulting in reduced PTS severity; however, these observations have not been rigorously validated. A multidisciplinary expert panel meeting was convened to plan a multicenter randomized controlled clinical trial to evaluate endovascular therapy for the treatment of advanced PTS. This article summarizes the findings of the panel, and is expected to assist in developing a National Institutes of Health-sponsored clinical trial and other studies to improve the care of patients with advanced PTS. PMID:27247235

  9. Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance.

    PubMed

    Palumbo, Antonio; Palladino, Carmela

    2012-10-01

    Oral immunomodulatory drugs (IMiDs), namely thalidomide, lenalidomide and pomalidomide, interfere with several pathways important for disease progression. Today they play a crucial role in the treatment of multiple myeloma patients, and have considerably improved myeloma outcomes. These agents, and thalidomide in particular, are associated with higher rates of thromboembolic events, both venous and arterial. Individual risk factors for thromboembolic events include advanced age, previous history of thromboembolism, an indwelling central venous catheter, comorbid conditions (e.g. infections, diabetes, cardiac disease, obesity), current or recent immobilization, recent surgery and inherited thrombophilic abnormalities. Cancer therapy and cancer itself also increase the risk of thromboembolic events. The aim of this review is to help clinicians to define the risk of thrombotic events in patients treated with thalidomide and thus to provide practical recommendations to manage thromboprophylaxis in these patients.

  10. Non-Bacterial Thrombotic Endocarditis in a Patient with Rheumatoid Arthritis

    PubMed Central

    Choi, Jung-Hye; Park, Jeong-Eun; Kim, Jang-Young

    2016-01-01

    Rheumatoid arthritis (RA) is frequently associated with various extra-joint complications. Although rare, thromboembolic complications are associated with high morbidity and mortality. We experienced a very rare case of nonbacterial thrombotic endocarditis (NBTE) and subsequent embolic stroke in a patient with RA. A 72-year-old male with a 15-year history of RA suddenly developed neurologic symptoms of vomiting and dizziness. Brain magnetic resonance imaging revealed recently developed multiple cerebellar and cerebral lacunar infarctions. Echocardiography showed a pulsating mitral valve vegetation involving the posterior cusp of the mitral valve leaflet, which was confirmed as NBTE. Immediate anti-coagulation therapy was started. The NBTE lesion disappeared in follow-up echocardiography after 4 weeks of anti-coagulation treatment. PMID:27275182

  11. Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

    PubMed Central

    Bleeker, Jonathan S.; Hogan, William J.

    2011-01-01

    Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

  12. Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance

    PubMed Central

    Palladino, Carmela

    2012-01-01

    Oral immunomodulatory drugs (IMiDs), namely thalidomide, lenalidomide and pomalidomide, interfere with several pathways important for disease progression. Today they play a crucial role in the treatment of multiple myeloma patients, and have considerably improved myeloma outcomes. These agents, and thalidomide in particular, are associated with higher rates of thromboembolic events, both venous and arterial. Individual risk factors for thromboembolic events include advanced age, previous history of thromboembolism, an indwelling central venous catheter, comorbid conditions (e.g. infections, diabetes, cardiac disease, obesity), current or recent immobilization, recent surgery and inherited thrombophilic abnormalities. Cancer therapy and cancer itself also increase the risk of thromboembolic events. The aim of this review is to help clinicians to define the risk of thrombotic events in patients treated with thalidomide and thus to provide practical recommendations to manage thromboprophylaxis in these patients. PMID:25083240

  13. Cerebral thrombotic complications in adolescent leukemia/lymphoma patients treated with L-asparaginase-containing chemotherapy.

    PubMed

    Imamura, Toshihiko; Morimoto, Akira; Kato, Ryuichi; Izumi, Moriatu; Murakami, Aki; Matuo, Satoshi; Kiyosawa, Nobuyuki; Kano, Gen; Yoshioka, Hiroshi; Sugimoto, Tohru; Imashuku, Shinsaku

    2005-05-01

    We described the cerebral thrombotic complications developed in 2 adolescent patients treated with L-asparaginase-containing regimens. For determining risk factors, we retrospectively analysed hemostatic markers in 19 pediatric patients with leukemia or lymphoma who were treated with either 1 of the 2 L-asparaginase-containing regimens; 11 were treated with VLP1 and the remaining 8 were treated with the VLAD protocol. The data indicated that low coagulation factors in association with increased plasma D-dimer levels during or post-L-asparaginase administration combined with fresh frozen plasma infusion might have activated coagulation processes in these patients. Careful management is required to prevent such episodes in patients with markedly decreased coagulation factors and increased D-dimer levels following L-asparaginase administration.

  14. Diagnostic ramifications of ocular vascular occlusion as a first thrombotic event associated with factor V Leiden and prothrombin gene heterozygosity

    PubMed Central

    Schockman, Samantha; Glueck, Charles J; Hutchins, Robert K; Patel, Jaykumar; Shah, Parth; Wang, Ping

    2015-01-01

    Aim This study aimed to assess the diagnostic ramifications of vascular occlusion of the ocular vein and artery as a first thrombotic event associated with factor V Leiden (FVL) and/or prothrombin gene (PTG) heterozygosity. Methods Patients with ocular vein (n=191) and artery (n=74) occlusion, free of cardioembolic etiologies, were sequentially referred from vitreoretinal specialists for measurement of thrombophilia-hypofibrinolysis and compared to 110 healthy normal controls. Results Of the 265 patients, 29 (11%; 17 women, 12 men) of all referred ocular vascular occlusion (OVO) cases were found to be heterozygous for FVL and/or PTG, including 16 with FVL, 12 with PTG, and 1 with both. Of the 29 cases, 16 had central retinal vein occlusion (CRVO), 2 branch retinal vein occlusion (BRVO), 5 nonarteritic anterior ischemic optic neuropathy (NA-AION), 3 retinal artery occlusion (RAO), 2 amaurosis fugax (AF), and 1 had both CRVO and RAO. Of the 16 FVL cases, 15 (94%) had OVO as a first thrombotic event without prior deep venous thrombosis (DVT) or pulmonary embolism (PE); 6 (38%) also had other thrombotic events, including recurrent miscarriage, osteonecrosis, ischemic stroke, and/or ischemic colitis; and 5 (31%) had immediate family members with previous venous thromboembolism (VTE). Of the 12 PTG cases, 9 (75%) had OVO as a first thrombotic event, 5 (42%) experienced VTE other than DVT or PE, and 6 (50%) had immediate family members with VTE. In one patient with both FVL and PTG, DVT occurred before BRVO. Of the 17 women with FVL and/or PTG mutations, 7 (41%) experienced ≥1 miscarriage, 6 (35%) were on estrogen therapy, and 1 (6%) was on clomiphene. Conclusion Of the 265 patients with OVO, 29 (11%) had FVL and/or PTG, and 83% of these 29 cases presented with OVO as their first thrombotic event. By diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy. PMID:25897198

  15. Thrombotic Microangiopathy In Metastatic Melanoma Patients Treated with Adoptive Cell Therapy and Total Body Irradiation

    PubMed Central

    Tseng, Jennifer; Citrin, Deborah E.; Waldman, Meryl; White, Donald E.; Rosenberg, Steven A.; Yang, James C.

    2014-01-01

    Background Thrombotic microangioapathy (TMA) is a complication that developed in some patients receiving 12 Gy total body irradiation in addition to lymphodepleting preparative chemotherapy prior to infusion of autologous tumor infiltrating lymphocytes (TIL) with high-dose aldesleukin (IL-2). This paper describes the incidence, presentation and course of radiation-associated TMA. Methods The data for patients with metastatic melanoma who received ACT with TIL plus aldesleukin following myeloablative chemotherapy and 12 Gy total body irradiation was examined, looking at patient characteristics and the natural history of TMA. Results The median time to presentation was approximately 8 months after completing TBI. The estimated cumulative incidence of TMA was 31.2% (median follow-up of 24 months). Noninvasive criteria for diagnosis included newly elevated creatinine levels, new-onset hypertension, new-onset anemia, microscopic hematuria, thrombocytopenia, low haptoglobin and elevated lactate dehydrogenase values. Once diagnosed, patients were managed with control of their hypertension with multiple agents and supportive red blood cell transfusions. TMA typically stabilized or improved and no patient progressed to dialysis. TMA was associated with a higher probability of an anti-tumor response. Conclusions Thrombotic microangiopathy occurs in approximately a third of patients treated with a lymphodepleting preparative chemotherapy regimen with total body irradiation prior to autologous T-cell therapy. The disease has a variable natural history, however no patient developed end-stage renal failure. Successful management with supportive care and aggressive hypertension control is vital to the safe application of a systemic therapy that has shown curative potential for patients with disseminated melanoma. PMID:24474396

  16. Future therapeutic directions for factor Xa inhibition in the prophylaxis and treatment of thrombotic disorders.

    PubMed

    Turpie, Alexander G G

    2003-11-15

    The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy. PMID:14650863

  17. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    PubMed

    Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

    2015-01-01

    Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

  18. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2 Acquiring... each holds half of V's shares. Therefore, A and B each control V (see § 801.1(b)), and V is included...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the...

  19. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2 Acquiring... each holds half of V's shares. Therefore, A and B each control V (see § 801.1(b)), and V is included...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the...

  20. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the person(s.... Examples: 1. Corporation A (the ultimate parent entity included within person “A”) proposes to acquire Y, a... to be carried out by merging Y into X, a wholly-owned subsidiary of A, with X surviving, and...

  1. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the person(s.... Examples: 1. Corporation A (the ultimate parent entity included within person “A”) proposes to acquire Y, a... to be carried out by merging Y into X, a wholly-owned subsidiary of A, with X surviving, and...

  2. Acquiring and Organizing Curriculum Materials.

    ERIC Educational Resources Information Center

    Lare, Gary A.

    This book addresses two areas of need in a curriculum materials center--where to find curriculum materials for acquisition and how to organize these materials for efficient and effective access once they are acquired. The book is arranged in two parts: "Acquiring and Organizing the Collection" and "Resources." The book brings together many…

  3. Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk

    PubMed Central

    Reshef, A; Zanichelli, A; Longhurst, H; Relan, A; Hack, C E

    2015-01-01

    Background Recommended management of attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (C1-INH-HAE) includes therapy with exogenous C1INH. Thrombotic/thromboembolic events (TEE) have been reported with plasma-derived C1INH, but so far none with recombinant human C1INH (rhC1INH). This phase III, randomized, placebo (saline)-controlled study evaluated the safety of rhC1INH 50 IU/kg for the treatment of acute attacks in 74 patients with C1-INH-HAE. Methods Monitoring for TEE and assessment of risk of deep vein thrombosis (DVT) by the Wells prediction rule were performed, and levels of fibrin degradation products (plasma D-dimers) were assessed before study drug administration (baseline), 2 h, and 7 days posttreatment. Results Plasma D-dimer levels were elevated in 80% of the patients (median [25th–75th percentiles]: 2149 [480–5105] μg/l; normal ≤250 μg/l) and were higher in patients with submucosal (abdominal, oropharyngeal–laryngeal) attacks (3095 [890–10000] μg/l; n = 29) compared with subcutaneous (peripheral, facial) attacks (960 [450–4060] μg/l; n = 35). Median plasma D-dimer levels were comparable across treatment groups at baseline (1874 [475–4568] μg/l rhC1INH; 2259 [586–7533] μg/l saline) and 2 h postinfusion (2389 [760–4974] μg/l rhC1INH; 2550 [310–8410] μg/l saline); median plasma D-dimer levels were decreased by Day 7 in both groups (425 [232–3240] μg/l rhC1INH; 418 [246–2318] μg/l saline). No increased risk of DVT was identified, nor any TEE reported in rhC1INH treated or controls. Conclusion Elevated plasma D-dimer levels were associated with acute C1-INH-HAE attacks, particularly with submucosal involvement. However, rhC1INH therapy was not associated with thrombotic events. PMID:25640891

  4. Advances and challenges in the management of complement-mediated thrombotic microangiopathies

    PubMed Central

    van de Kar, Nicole C. A. J.

    2015-01-01

    Complement activation plays a major role in several renal pathophysiological conditions. The three pathways of complement lead to C3 activation, followed by the formation of the anaphylatoxin C5a and the terminal membrane attack complex (MAC) in blood and at complement activating surfaces, lead to a cascade of events responsible for inflammation and for the induction of cell lysis. In case of ongoing uncontrolled complement activation, endothelial cells activation takes place, leading to events in which at the end thrombotic microangiopathy can occur. Atypical haemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by excessive complement activation on the surface of the microcirculation. It is a severe, rare disease which leads to end-stage renal failure (ESRF) and/or to death in more than 50% of patients without treatment. In the first decade of the second millennium, huge progress in understanding the aetiology of this disease was made, which paved the way to better treatment. First, protocols of plasma therapy for treatment, prevention of relapses and for renal transplantation in those patients were set up. Secondly, in some severe cases, combined kidney and liver transplantation was reported. Finally, at the end of this decade, the era of complement inhibitors, as anti-C5 monoclonal antibody (anti-C5 mAb) began. The past five years have seen growing evidence of the favourable effect of anti-C5 mAb in aHUS which has made this drug the first-line treatment in this disease. The possible complication of meningococcal infection needs appropriate vaccination before its use. Unfortunately, the worldwide use of anti-C5 mAb is limited by its very high price. In the future, extension of indications for anti-C5 mAb use, the elaboration of generics and of mAbs directed towards other complement factors of the terminal pathway of the complement system might succeed in reducing the cost of this new valuable therapeutic approach and render it available

  5. Thrombotic events in MYH9 gene-related autosomal macrothrombocytopenias (old May-Hegglin, Sebastian, Fechtner and Epstein syndromes).

    PubMed

    Girolami, Antonio; Antonio, Girolami; Vettore, Silvia; Silvia, Vettore; Bonamigo, Emanuela; Emanuela, Bonamigo; Fabris, Fabrizio; Fabrizio, Fabris

    2011-11-01

    Congenital macrothrombocytopenia are a group of disorders which may be due to mutations in the MYH9 gene. This gene linked to chromosome 22 encodes for the nonmuscle heavy chain IIA that is expressed in platelets and in other tissues. In the past these disorders were known as May-Hegglin anomaly, Sebastian, Fechtner and Epstein syndromes. The main common feature is the presence of thrombocytopenia with large platelets. The evaluation of all reported cases indicates that thrombotic events appear to occur only in patients with May Hegglin variants. Whether this is due to the higher prevalence of this variant as compared with the others or to a specific difference is still unknown. However, the occurrence of thrombotic events in only one of these conditions may be used as a new tentative differentiability feature.

  6. Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.

    PubMed

    Harenberg, Job

    2016-04-01

    A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs. PMID:27067972

  7. [Characteristic of fatal thrombotic complications based on the materials from the Thanatology Department of Forensic Medicine Bureau of the Rostov region, for 2004-2007].

    PubMed

    Berezovskiĭ, D P; Kolkutin, V V; Kovtunov, V V; Kornienko, I V

    2009-01-01

    The authors report statistical data on the spectrum and frequency of fatal thrombotic complications based on the analysis of materials available from the regional bureau of forensic medical examination collected in the period from 2004 to 2007. All lethal cases are categorized in terms of the patients' age, gender, time and clinical characteristics of the injury, time of surgical intervention. Results of the analysis indicate the necessity of examination of fatal cases of thrombotic complications following a standardized protocol.

  8. Thrombotic Occlusion of Stent Graft Limbs due to Severe Angulation of Aortic Neck in Endovascular Repair of Abdominal Aortic Aneurysm

    PubMed Central

    Kim, Minsu; Kim, Myeong Gun; Oh, Pyung Chun; Lee, Ji Yeon; Kang, Jin Mo; Chung, Wook-Jin; Shin, Eak Kyun

    2016-01-01

    Endovascular aneurysm repair (EVAR) is a safe alternative to open surgical repair for an abdominal aortic aneurysm. However, unfavorable aortic anatomy of the aneurysm has restricted the widespread use of EVAR. Anatomic limitation is most often related to characteristics of the proximal neck anatomy. In this report, we described a patient with a severely angulated proximal neck who underwent EVAR, but required repeat intervention because of thrombotic occlusion of stent graft limbs. PMID:27721866

  9. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).

    PubMed

    Korkmaz, Huseyin; Bugdaci, Mehmet Sait; Temel, Tuncer; Dagli, Mehmet; Karabagli, Pinar

    2013-04-01

    Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

  10. Anti-thrombotic effect of a novel formula from Corni fructus with malic acid, succinic acid and citric acid.

    PubMed

    Zhang, Qi-Chun; Zhao, Yue; Bian, Hui-Min

    2014-05-01

    Our previous investigation had confirmed the inhibition of platelet aggregation of a novel Corni fructus-derived formula composed of malic acid, succinic acid and citric acid with a ratio of 3:2:2. The present study was to further evaluate the anti-thrombotic effect of the formula in vivo. Mice of acute pulmonary thromboembolism, and rats of arterial thrombosis were used to determine the anti-thrombotic effect of the formula. Histology analysis of endothelium was conducted with hematoxylin and eosin stain. TXB2 , 6-K-PGF1α , cAMP, cGMP and NO in rat plasma were determined. In vitro assay of αIIbβ3 and phosphorylation of ERK1/2 were performed in ADP-treated platelet. The formula significantly reduced the recovery time and mortality rate of mice with acute pulmonary thromboembolism. Remarkably extended occlusion time, decreased thrombus weight and more integrated endothelium were observed in rat with the formula. Enhanced 6-K-PGF1α , cGMP and NO, but not TXB2 and cAMP, were demonstrated in rat plasma with treatment of the formula. Finally, the formula was shown to inhibit αIIbβ3 expression and activation of ERK1/2 in platelet. The formula shows positive anti-thrombotic effect. The direct interference on ADP activated signaling in platelet and regulation of endothelium function are two primary pathways involved in the action on thrombosis.

  11. Unbiased pro-thrombotic features at diagnosis in 977 thrombocythemic patients with Philadelphia-negative chronic myeloproliferative neoplasms.

    PubMed

    Gugliotta, Luigi; Iurlo, Alessandra; Gugliotta, Gabriele; Tieghi, Alessia; Specchia, Giorgina; Gaidano, Gianluca; Scalzulli, Potito R; Rumi, Elisa; Dragani, Alfredo; Martinelli, Vincenzo; Santoro, Cristina; Randi, Maria Luigia; Tagariello, Giuseppe; Candoni, Anna; Cattaneo, Daniele; Ricco, Alessandra; Palmieri, Raffaele; Liberati, Marina A; Langella, Maria; Rago, Angela; Bergamaschi, Micaela; Monari, Paola; Miglio, Rossella; Santoro, Umberto; Cacciola, Rossella; Rupoli, Serena; Mastrullo, Lucia; Musto, Pellegrino; Mazzucconi, Maria Gabriella; Vignetti, Marco; Cortelezzi, Agostino; Vianelli, Nicola; Martino, Bruno; De Stefano, Valerio; Passamonti, Francesco; Vannucchi, Alessandro M

    2016-07-01

    In patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), the anti-thrombotic and/or cytoreductive treatment in the follow-up may affect the evaluation of the pro-thrombotic weight of the clinical and biological characteristics at diagnosis. In order to avoid this potential confounding effect, we investigated the relationship between prior thrombosis (PrTh: thrombosis occurred before diagnosis and before treatment) and the characteristics at diagnosis in 977 thrombocythemic patients with MPN, reclassified according to the WHO 2008 criteria. PrTh occurred in 194 (19.9%) patients, with similar rates in the different MPNs. In multivariate analysis, PrTh rate was significantly related to minor thrombocytosis (platelets ≤700×10(9)/L), leukocytosis (leukocytes >10×10(9)/L), higher hematocrit (HCT >45%), JAK2 V617F mutation, older age, and cardiovascular risk factors (CVRFs). The highest PrTh rate (33.9%) was associated with the coexistence of minor thrombocytosis and leukocytosis. Of note, the inverse relationship between PrTh rate and platelet count is consistent with the hemostatic paradox of thrombocytosis. In conclusion, this analysis in MPN patients disclosed the unbiased characteristics at diagnosis with a pro-thrombotic effect. Moreover, it suggests that the optimal control of blood cells counts, and CVRFs might be of utmost importance in the prevention of thrombosis during the follow-up. PMID:27107744

  12. Flow cytometric analysis of thiazole orange uptake by platelets: a diagnostic aid in the evaluation of thrombocytopenic disorders.

    PubMed

    Kienast, J; Schmitz, G

    1990-01-01

    Thiazole orange (TO), a fluorescent dye originally synthesized for reticulocyte analysis, is characterized by a large fluorescence enhancement and high quantum yield on binding to nucleic acids, particularly RNA. In addition, the dye readily permeates live cell membranes. We applied TO staining, followed by fluorescence-activated flow cytometric analysis, to platelets in whole blood samples from hematologically normal subjects and patients with various quantitative platelet disorders. The percentage of TO-positive platelets in 50 control subjects was 8.6 +/- 2.8% (mean +/- SD) ranging from 2.8% to 15.8%. In 21 thrombocytopenic patients whose bone marrow contained normal to increased numbers of megakaryocytes, the percentage of fluorescently labeled platelets was significantly elevated (P less than .0001) to 26.9 +/- 10.9% (range, 13.3% to 57.1%). In contrast, the proportion of positively stained platelets in 23 patients with thrombocytopenia due to impaired platelet production (various conditions with reduced marrow megakaryocytes) did not significantly differ from the controls, whereas the absolute counts of TO-positive platelets were significantly lowered (P less than .0001). Differences in the distributions of the percentage values as well as of the absolute counts for TO-positive platelets between the two patient groups were again highly significant (P less than .0001). Both the sensitivity and the specificity of this method in distinguishing between these categories of thrombocytopenia were greater than or equal to 95%. We conclude that flow cytometric analysis of platelets after staining with TO is a sensitive and specific test that rapidly provides information on the thrombopoietic activity in thrombocytopenic disorders. Our data further suggest that increased amounts of residual RNA characterize platelets released under conditions of "stress thrombopoiesis."

  13. Endocardial Endothelial Dysfunction Progressively Disrupts Initially Anti then Pro-Thrombotic Pathways in Heart Failure Mice

    PubMed Central

    Schoner, Amanda; Tyrrell, Christina; Wu, Melinda; Gelow, Jill M.; Hayes, Alicia A.; Lindner, Jonathan R.; Thornburg, Kent L.; Hasan, Wohaib

    2015-01-01

    Objective An experimental model of endocardial thrombosis has not been developed and endocardial endothelial dysfunction in heart failure (HF) is understudied. We sought to determine whether disruption of the endothelial anti-coagulant activated protein C (APC) pathway in CREBA133 HF mice promotes endocardial thrombosis in the acute decompensated phase of the disease, and whether alterations in von Willebrand factor (vWF) secretion from HF endocardium reduces thrombus formation as HF stabilizes. Approach and results Echocardiography was used to follow HF development and to detect endocardial thrombi in CREBA133 mice. Endocardial thrombi incidence was confirmed with immunohistochemistry and histology. In early and acute decompensated phases of HF, CREBA133 mice had the highest incidence of endocardial thrombi and these mice also had a shorter tail-bleeding index consistent with a pro-thrombotic milieu. Both APC generation, and expression of receptors that promote APC function (thrombomodulin, endothelial protein C receptor, protein S), were suppressed in the endocardium of acute decompensated HF mice. However, in stable compensated HF mice, an attenuation occurred for vWF protein content and secretion from endocardial endothelial cells, vWF-dependent platelet agglutination (by ristocetin), and thrombin generation on the endocardial surface. Conclusions CREBA133 mice develop HF and endocardial endothelial dysfunction. Attenuation of the anti-coagulant APC pathway promotes endocardial thrombosis in early and acute decompensated phases of HF. However, in stable compensated HF mice, disruptions in endothelial vWF expression and extrusion may actually reduce the incidence of endocardial thrombosis. PMID:26565707

  14. The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity

    PubMed Central

    Ampofo, Emmanuel; Später, Thomas; Müller, Isabelle; Eichler, Hermann; Menger, Michael D.; Laschke, Matthias W.

    2015-01-01

    Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound. PMID:26569265

  15. Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid antibodies

    PubMed Central

    Seshan, Surya V.; Franzke, Claus-Werner; Redecha, Patricia; Monestier, Marc; Mackman, Nigel

    2009-01-01

    Using different mouse monoclonal and human antiphospholipid (aPL) antibodies, we developed a new animal model of renal injury that shares many features with thrombotic microangiopathy (TMA). We found that more than 1 mechanism/signaling pathway is involved in glomerular injury induced by aPL antibodies in this model. Both complement-dependent and complement-independent pathways were identified that lead to glomerular endothelial cell damage and renal function impairment. We also found that C5a-C5aR interaction is a crucial step for the activation of the coagulation cascade and glomerular injury induced by complement-activating antibodies. In addition, our studies demonstrated complement-independent mechanisms in which reactivity with β2 glycoprotein I (β2GPI) plays an important role in aPL-induced glomerular damage and renal failure. Independently of the mechanism responsible for aPL-induced TMA, mice that express low levels of tissue factor (TF) were protected from glomerular injury. That genetic reduction of TF prevents renal injury induced by different aPL antibodies indicates that TF is a common mediator of glomerular damage and a possible target for selective pharmacologic intervention. Treatment with pravastatin, which down-regulates glomerular TF synthesis, prevents aPL-induced TMA in this mouse model, thus emphasizing that targeting TF might be a good therapeutic intervention in patients with TMA. PMID:19535796

  16. Inherited DNA mutations contributing to thrombotic complications in patients with sickle cell disease.

    PubMed

    Zimmerman, S A; Ware, R E

    1998-12-01

    Thrombosis may play an important role in the pathophysiology of certain complications of sickle cell disease (SCD), including stroke and avascular necrosis (AVN). Currently there is no laboratory or clinical parameter that can identify patients who are at highest risk of developing these thrombotic complications. We hypothesized that some patients with SCD have an inherited hypercoagulable state that results in an increased risk of developing stroke or AVN. We examined the role of two common inherited thrombophilic mutations that, in other populations, have been associated with arterial and venous thrombosis and are amenable to screening with DNA restriction enzyme analysis. The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the C1565T mutation in the platelet glycoprotein IIIa (GPIIIa) gene were evaluated. We analyzed genomic DNA from 86 children and adults with SCD, including 16 patients with a history of a clinical stroke and 14 patients with AVN, for the presence of these mutations. The C677T MTHFR mutation was found in 19% of patients with stroke, 14% of patients with AVN, and 14% of patients with neither complication (P = NS). The C1565T GPIIIa mutation was found in 25% of patients with stroke, 14% of patients with AVN, and 18% of patients with neither complication (P = NS). Although each of these mutations is relatively common in patients with SCD, neither is independently associated with an increased risk of developing stroke or AVN. PMID:9840906

  17. Excellent long-term results with iliac stenting in local anesthesia for post-thrombotic syndrome

    PubMed Central

    Just, Sven; Foegh, Pia; Baekgaard, Niels

    2015-01-01

    Background Only 20% of iliac veins will recanalize on anticoagulation (AC) treatment alone and may, therefore, develop venous obstruction after iliofemoral deep venous thrombosis (DVT). A considerable number of these patients will suffer from post-thrombotic syndrome (PTS) leading to impaired quality of life in more than 50%. Endovascular treatment for iliac vein obstruction using stents is known to alleviate PTS symptoms in selected patients. Purpose To report the Danish long-term results of endovascular treatment with iliac stenting. Material and Methods From 2000 to 2013 consecutive patients were evaluated and 19 patients with severe venous claudication were identified and subsequently underwent angioplasty and stenting. AC treatment was prescribed for 6 months, and knee-high class II compression stocking recommended for 1 year. Scheduled follow-up was done in the outpatient clinic at 6 weeks, 3 months, and annually thereafter. Results Nineteen patients, all women, all with left-sided iliac vein obstruction, and all with severe PTS symptoms were included. The median follow-up time was 81 months (range, 1–146 months; mean, 69 months). Primary patency rate of the inserted iliac stent was 89% (17/19) and 16 patients (84 %) had almost or total symptom relief at follow-up. Conclusion Endovascular stenting of iliac obstruction in local anesthesia is minimally invasive and shows excellent long-term outcomes for patients suffering from PTS. PMID:26445677

  18. Left atrial strain: a new predictor of thrombotic risk and successful electrical cardioversion

    PubMed Central

    González-Alujas, Teresa; Valente, Filipa; Aranda, Carlos; Rodríguez-Palomares, José; Gutierrez, Laura; Maldonado, Giuliana; Galian, Laura; Teixidó, Gisela; Evangelista, Artur

    2016-01-01

    Background Left atrial deformation (LAD) parameters are new markers of atrial structural remodelling that seem to be affected in atrial fibrillation (AF) and atrial flutter (AFL). This study aimed to determine whether LAD can identify patients with a higher risk of thrombosis and unsuccessful electrical cardioversion (ECV). Methods Retrospective study including 56 patients with AF or AFL undergoing ECV, with previous transthoracic (TTE) and transoesophageal echocardiography (TEE) studies. Echocardiographic parameters analysed were as follows: left ventricle function, left atrium (LA) dimensions, LAD parameters (positive and negative strain peaks), left atrial appendage (LAA) filling and emptying velocities and the presence of thrombi. Strain values were analysed according to thrombotic risk and success of ECV. Results Lower mean values of peak-positive strain (PPS) in patients with prothrombotic velocities (<25 cm/s) and a higher incidence of thrombi in LAA were observed compared with those with normal velocities. Multivariate analysis revealed PPS normalised by LA maximum volume indexed by body surface area (BSA) to be associated with prothrombotic risk (odds ratio 0.000 (95% CI: 0.000–0.243), P 0.017), regardless of CHADs2VASC score. Peak-negative strain normalised by LA volumes indexed by BSA were associated with unsuccessful ECV. Conclusions Atrial deformation parameters identify AF and AFL patients with a high risk of thrombosis and unsuccessful ECV. Therefore, these new parameters should be included in anticoagulation management and rhythm vs rate control strategies. PMID:27249551

  19. Ischemic myocardial disease as an example of a thrombotic event. A historical note.

    PubMed

    Martins e Silva, J

    2006-05-01

    The definition of myocardial ischemia as a clinical entity of thrombotic etiology was established in 1912 by James Herrick. His proposal was based on the work of William Heberden, who in 1772 defined the clinical profile of angina pectoris, and the observations of Edward Jenner about a century later on intracoronary thrombosis in patients who had died with such symptoms. On the basis of these results, Jenner and Caleb Parry proposed that the main cause of angina were alterations in the coronary arteries, while Marshall Hall, in 1842, attributed sudden death in these patients to interruption of the coronary circulation. The discovery of a common cause for angina pectoris and myocardial infarction, inducing a reduction or interruption of oxygen supply to myocardial tissue, the atherosclerotic etiology of intracoronary lesions, and the importance of plaque fissuring in the sudden formation of intracoronary thrombi, were successive milestones in our understanding in the 20th century, the culmination of the process of meticulous observation begun many years before. PMID:16910161

  20. Von Willebrand Factor-Cleaving Protease Activity in Thrombotic Microangiopathy: First Report From Iran

    PubMed Central

    Ardalan, Mohammadreza; Rezaeifar, Parisa

    2014-01-01

    Background: Thrombotic microangiopathy (TMA) is a rare but devastating small vessels disorder that is characterized by intravascular platelet thrombi, thrombocytopenia, and various degrees of organ ischemia and anemia, which is due to erythrocyte fragmentation in microcirculation. Objectives: The Aim of this study was to determine the von Willebrand factor-cleaving protease (ADAMTS13) activity during the acute phase of TMA. We also investigated inhibiting antibodies against ADAMTS13 in these patients. Patients and Methods: In a collaborative work with Mario-Negro institute of pharmacological research in Bergamo-Italy, we registered the clinical and laboratory data, collected the serum samples, and transferred the samples to the laboratories. Serum samples were taken before the start of plasmapheresis or at least 15 days after the final exchange. Results: We recruited 40 patients (14 males and 26 females) with the mean age of 46.12 ± 17.26 years. The mean activity of ADAMTS13 was 34.58% ± 21.83%. Two patients had inhibitory antibodies against ADAMTS13 with profound deficiency of ADAMTS13 activity (< 6%). Infectious diseases were the most common underlying condition, followed by systemic lupus erythematous. Conclusions: Majority of patients had an underlying condition and had various ADAMTS13 activity. The presence of inhibiting antibodies and accompanied complete deficiency of ADAMTS13 activity is an indicator of severity. PMID:25738110

  1. Eosinophilic Granulomatosis With Polyangiitis With Thrombotic Microangiopathy: Is Simultaneous Systemic Lupus Erythematosus Associated With Clinical Manifestations?

    PubMed Central

    Fukui, Shoichi; Iwamoto, Naoki; Tsuji, Sosuke; Umeda, Masataka; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Horai, Yoshiro; Koga, Tomohiro; Kawashiri, Shin-ya; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Kinoshita, Naóe; Kawakami, Atsushi

    2015-01-01

    Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is one of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which is characterized by vasculitis of the small to medium-sized vessels. On the contrary, thrombotic microangiopathy (TMA) is a life-threatening condition which can cause ischemic organ injury. Although several case reports have described patients with TMA associated with ANCA-associated vasculitis except for EGPA, there are no previous case reports of EGPA associated with TMA. A 71-year-old Japanese man was diagnosed with EGPA based on his asthma, eosinophilia, lung opacity, refractory sinusitis, and positive myeloperoxidase-ANCA. He was also diagnosed with TMA based on peripheral schizocytes and hemolytic anemia. We performed plasmapheresis and started high-dose corticosteroid therapy; thereafter, he improved promptly. His case also fulfilled the classification criteria of systemic lupus erythematosus (SLE) based on the pleural effusion, renal disorder, anemia, thrombocytopenia, positive antidouble-stranded DNA antibody, and low complement. Elements of SLE were thought to affect his clinical course. We reviewed 11 patients with EGPA or hypereosinophilic syndrome (HES) associated with SLE, including our case. Patients with EGPA or HES associated with SLE had more heart complications than patients with simple EGPA or simple HES did. Patients with EGPA or HES associated with SLE had more pleural effusion than patients with simple SLE did. Clinical manifestations of eosinophilia with SLE or SLE with eosinophilia may differ from simple SLE or simple eosinophilia. PMID:26559264

  2. A Clinicopathologic Study of Thrombotic Microangiopathy in IgA Nephropathy

    PubMed Central

    Hill, Gary S.; Karras, Alexandre; Jacquot, Christian; Moulonguet, Luc; Kourilsky, Olivier; Frémeaux-Bacchi, Véronique; Delahousse, Michel; Van Huyen, Jean-Paul Duong; Loupy, Alexandre; Bruneval, Patrick; Nochy, Dominique

    2012-01-01

    Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes. PMID:22052055

  3. Comparative pharmacokinetics of five rhubarb anthraquinones in normal and thrombotic focal cerebral ischemia-induced rats.

    PubMed

    Feng, Su-xiang; Li, Jian-sheng; Qu, Ling-bo; Shi, Yan-mei; Zhao, Di

    2013-10-01

    A comparative oral pharmacokinetic study of five anthraquinones (aloe-emodin, emodin, rhein, chrysophanol and physcion) from the extract of Rheum palmatum L. was performed in normal and thrombotic focal cerebral ischemia (TFCI)-induced rats. The plasma samples were clarified through solid phase extraction prior to simultaneous determination of the anthraquinones with a validated high-performance liquid chromatography-fluorescence system. The results indicated that the Cmax, t(1/2) and AUC(0-t), of aloe-emodin, rhein, emodin and chrysophanol in TFCI-induced rats were nearly double, whereas the CL values were remarkably decreased (p < 0.05) over those of the normal rats. The plasma drug concentration-time data of five anthraquinones to rats fitted a two-compartment open model. The five anthraquinones in rat plasma were absorbed quickly and eliminated slowly in both groups. The obtained results could be helpful for evaluating the impact of the efficacy and safety of the drug in clinical applications.

  4. Surgical revascularisation in patients with severe limb ischaemia induces a pro-thrombotic state.

    PubMed

    Collins, P; Ford, I; Greaves, M; Macaulay, E; Brittenden, J

    2006-08-01

    Platelet and coagulation activation are implicated in the increased incidence of ischaemic events seen in patients with peripheral arterial disease. This study aimed to assess the effect of surgical revascularisation on platelet aggregation and coagulation in patients with severe limb ischaemia (SLI). Twenty-two patients had blood samples taken: prior to surgery, on reperfusion, 2, 24 and 48 h post-surgery. Platelet aggregation through COX-mediated and thrombin receptor activator peptide (TRAP)-stimulated GPIIb/IIIa pathways was measured by the Ultegra point of care system. Thrombin-antithrombin III Complex (TAT) and D-dimer were measured by ELISA. COX-mediated aggregation increased significantly at reperfusion and remained elevated at 24 h [median increase from baseline of 9% (range -16 to 33%) P = 0.011]. TRAP-stimulated aggregation increased significantly at reperfusion and remained elevated at 2 h post-surgery [median increase 18% (range -71 to 45%); P = 0.007]. TAT levels were significantly elevated from reperfusion and remained so at 48 h (P < 0.003), whereas D-dimer only increased at 24 h (P = 0.014). For the first time, we have demonstrated that in patients with SLI, platelet aggregation is increased following surgery and there is a mismatch in the balance between the coagulation and fibrinolytic pathways despite the use of aspirin and heparin. Thus in the early post-operative these patients exhibit a pro-thrombotic state. PMID:16928603

  5. Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

    PubMed

    Boyers, Dwayne; Jia, Xueli; Jenkinson, David; Mowatt, Graham

    2012-06-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^⁹/L and 400 × 10^⁹/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed

  6. One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial

    PubMed Central

    Mol, G C; van de Ree, M A; Klok, F A; Tegelberg, M J A M; Sanders, F B M; Koppen, S; de Weerdt, O; Koster, T; Hovens, M M C; Kaasjager, H A H; Brouwer, R E; Kragten, E; Schaar, C G; Spiering, W; Arnold, W P; Biesma, D H

    2016-01-01

    Objective To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis. Design Multicentre single blind non-inferiority randomised controlled trial. Setting Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre. Participants Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg. Interventions Continuation or cessation of ECS 12 months after deep venous thrombosis. Main outcome measures The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym). Results 518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups. Conclusion Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non

  7. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders.

    PubMed

    Simeoni, Ilenia; Stephens, Jonathan C; Hu, Fengyuan; Deevi, Sri V V; Megy, Karyn; Bariana, Tadbir K; Lentaigne, Claire; Schulman, Sol; Sivapalaratnam, Suthesh; Vries, Minka J A; Westbury, Sarah K; Greene, Daniel; Papadia, Sofia; Alessi, Marie-Christine; Attwood, Antony P; Ballmaier, Matthias; Baynam, Gareth; Bermejo, Emilse; Bertoli, Marta; Bray, Paul F; Bury, Loredana; Cattaneo, Marco; Collins, Peter; Daugherty, Louise C; Favier, Rémi; French, Deborah L; Furie, Bruce; Gattens, Michael; Germeshausen, Manuela; Ghevaert, Cedric; Goodeve, Anne C; Guerrero, Jose A; Hampshire, Daniel J; Hart, Daniel P; Heemskerk, Johan W M; Henskens, Yvonne M C; Hill, Marian; Hogg, Nancy; Jolley, Jennifer D; Kahr, Walter H; Kelly, Anne M; Kerr, Ron; Kostadima, Myrto; Kunishima, Shinji; Lambert, Michele P; Liesner, Ri; López, José A; Mapeta, Rutendo P; Mathias, Mary; Millar, Carolyn M; Nathwani, Amit; Neerman-Arbez, Marguerite; Nurden, Alan T; Nurden, Paquita; Othman, Maha; Peerlinck, Kathelijne; Perry, David J; Poudel, Pawan; Reitsma, Pieter; Rondina, Matthew T; Smethurst, Peter A; Stevenson, William; Szkotak, Artur; Tuna, Salih; van Geet, Christel; Whitehorn, Deborah; Wilcox, David A; Zhang, Bin; Revel-Vilk, Shoshana; Gresele, Paolo; Bellissimo, Daniel B; Penkett, Christopher J; Laffan, Michael A; Mumford, Andrew D; Rendon, Augusto; Gomez, Keith; Freson, Kathleen; Ouwehand, Willem H; Turro, Ernest

    2016-06-01

    Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD.

  8. Thrombotic responses of endothelial outgrowth cells to protein-coated surfaces

    PubMed Central

    Anderson, Deirdre E. J.; McKenna, Kathryn A.; Glynn, Jeremy J.; Marzec, Ulla; Hanson, Stephen R.; Hinds, Monica T.

    2015-01-01

    There is significant clinical need for viable small-diameter vascular grafts. While there are many graft biomaterials in development, few have been clinically successful. Evaluation of grafts with a clinically-relevant model is needed to drive development. This work examined extracellular matrix coatings on the thrombotic phenotype of endothelial outgrowth cells (EOCs). EOCs were tested on flat plates and on tubular grafts. Flat plate studies examined collagen I, collagen IV, fibronectin, and α-elastin coatings. The EOCs attached or proliferated more readily on collagen I and fibronectin surfaces as determined by total DNA. The APC production by EOCs was also dependent on surface coating with collagen I and fibronectin displaying a higher activity than both collagen IV and α-elastin on flat plate studies. Based on these results, only collagen I and fibronectin coatings were tested on expanded poly(tetrafluoroethylene) (ePTFE) in the ex vivo model. Tubular samples showed significantly greater tissue factor pathway inhibitor gene expression on collagen I than on fibronectin. Platelet adhesion was not significantly different, but EOCs on collagen I produced significantly lower APC than on fibronectin, suggesting that differences exist between the flat plate and tubular cultures. Overall, while the hemostatic phenotype of the EOCs displayed some differences, cell responses were largely independent of the matrix coating. EOCs adhered strongly to both fibronectin and collagen I coated ePTFE grafts under ex vivo (100 mL/min) flow conditions suggesting the usefulness of this clinically-relevant cell source, testing modality, and shunt model for future work examining biomaterials and cell conditioning before implantation. PMID:25612682

  9. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders.

    PubMed

    Simeoni, Ilenia; Stephens, Jonathan C; Hu, Fengyuan; Deevi, Sri V V; Megy, Karyn; Bariana, Tadbir K; Lentaigne, Claire; Schulman, Sol; Sivapalaratnam, Suthesh; Vries, Minka J A; Westbury, Sarah K; Greene, Daniel; Papadia, Sofia; Alessi, Marie-Christine; Attwood, Antony P; Ballmaier, Matthias; Baynam, Gareth; Bermejo, Emilse; Bertoli, Marta; Bray, Paul F; Bury, Loredana; Cattaneo, Marco; Collins, Peter; Daugherty, Louise C; Favier, Rémi; French, Deborah L; Furie, Bruce; Gattens, Michael; Germeshausen, Manuela; Ghevaert, Cedric; Goodeve, Anne C; Guerrero, Jose A; Hampshire, Daniel J; Hart, Daniel P; Heemskerk, Johan W M; Henskens, Yvonne M C; Hill, Marian; Hogg, Nancy; Jolley, Jennifer D; Kahr, Walter H; Kelly, Anne M; Kerr, Ron; Kostadima, Myrto; Kunishima, Shinji; Lambert, Michele P; Liesner, Ri; López, José A; Mapeta, Rutendo P; Mathias, Mary; Millar, Carolyn M; Nathwani, Amit; Neerman-Arbez, Marguerite; Nurden, Alan T; Nurden, Paquita; Othman, Maha; Peerlinck, Kathelijne; Perry, David J; Poudel, Pawan; Reitsma, Pieter; Rondina, Matthew T; Smethurst, Peter A; Stevenson, William; Szkotak, Artur; Tuna, Salih; van Geet, Christel; Whitehorn, Deborah; Wilcox, David A; Zhang, Bin; Revel-Vilk, Shoshana; Gresele, Paolo; Bellissimo, Daniel B; Penkett, Christopher J; Laffan, Michael A; Mumford, Andrew D; Rendon, Augusto; Gomez, Keith; Freson, Kathleen; Ouwehand, Willem H; Turro, Ernest

    2016-06-01

    Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD. PMID:27084890

  10. Deficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy.

    PubMed

    Onclinx, Cécile; Dogne, Sophie; Jadin, Laurence; Andris, Fabienne; Grandfils, Christian; Jouret, François; Mullier, François; Flamion, Bruno

    2015-08-01

    Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are hyaluronidases 1 and 2, neither of which is active in the bloodstream. We generated hyaluronidase 2-deficient mice. These animals suffer from chronic, mild anemia and thrombocytopenia, in parallel with a 10-fold increase in plasma hyaluronan concentration. In this study we explored the mechanism of these hematologic anomalies. The decreased erythrocyte and platelet counts were attributed to peripheral consumption. The erythrocyte half-life was reduced from 25 to 8 days without signs of premature aging. Hyaluronidase 2-deficient platelets were functional. Major intrinsic defects in erythrocyte membrane or stability, as well as detrimental effects of high hyaluronan levels on erythrocytes, were ruled out in vitro. Normal erythrocytes transfused into hyaluronidase 2-deficient mice were quickly destroyed but neither splenectomy nor anti-C5 administration prevented chronic hemolysis. Schistocytes were present in blood smears from hyaluronidase 2-deficient mice at a level of 1% to 6%, while virtually absent in control mice. Hyaluronidase 2-deficient mice had increased markers of endothelial damage and microvascular fibrin deposition, without renal failure, accumulation of ultra-large multimers of von Willebrand factor, deficiency of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13 (ADAMTS13), or hypertension. There was no sign of structural damage in hepatic or splenic sinusoids, or in any other microvessels. We conclude that hyaluronidase 2 deficiency induces chronic thrombotic microangiopathy with hemolytic anemia in mice. The link between this uncommon condition and hyaluronidase 2 remains to be explored in humans.

  11. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

    PubMed Central

    Simeoni, Ilenia; Stephens, Jonathan C.; Hu, Fengyuan; Deevi, Sri V. V.; Megy, Karyn; Bariana, Tadbir K.; Lentaigne, Claire; Schulman, Sol; Sivapalaratnam, Suthesh; Vries, Minka J. A.; Westbury, Sarah K.; Greene, Daniel; Papadia, Sofia; Alessi, Marie-Christine; Attwood, Antony P.; Ballmaier, Matthias; Baynam, Gareth; Bermejo, Emilse; Bertoli, Marta; Bray, Paul F.; Bury, Loredana; Cattaneo, Marco; Collins, Peter; Daugherty, Louise C.; Favier, Rémi; French, Deborah L.; Furie, Bruce; Gattens, Michael; Germeshausen, Manuela; Ghevaert, Cedric; Goodeve, Anne C.; Guerrero, Jose A.; Hampshire, Daniel J.; Hart, Daniel P.; Heemskerk, Johan W. M.; Henskens, Yvonne M. C.; Hill, Marian; Hogg, Nancy; Jolley, Jennifer D.; Kahr, Walter H.; Kelly, Anne M.; Kerr, Ron; Kostadima, Myrto; Kunishima, Shinji; Lambert, Michele P.; Liesner, Ri; López, José A.; Mapeta, Rutendo P.; Mathias, Mary; Millar, Carolyn M.; Nathwani, Amit; Neerman-Arbez, Marguerite; Nurden, Alan T.; Nurden, Paquita; Othman, Maha; Peerlinck, Kathelijne; Perry, David J.; Poudel, Pawan; Reitsma, Pieter; Rondina, Matthew T.; Smethurst, Peter A.; Stevenson, William; Szkotak, Artur; Tuna, Salih; van Geet, Christel; Whitehorn, Deborah; Wilcox, David A.; Zhang, Bin; Revel-Vilk, Shoshana; Gresele, Paolo; Bellissimo, Daniel B.; Penkett, Christopher J.; Laffan, Michael A.; Mumford, Andrew D.; Rendon, Augusto; Freson, Kathleen; Ouwehand, Willem H.; Turro, Ernest

    2016-01-01

    Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD. PMID:27084890

  12. Experimental reversal of acute coronary thrombotic occlusion and myocardial injury in animals utilizing streptokinase.

    PubMed

    Lee, G; Giddens, J; Krieg, P; Dajee, A; Suzuki, M; Kozina, J A; Ikeda, R M; DeMaria, A N; Mason, D T

    1981-12-01

    Fresh autologous thrombus, 1.0 to 1.5 ml, was injected into the left anterior descending and/or left diagonal coronary arteries of 19 open-chest dogs to produce evolving acute myocardial infarction (AMI). Thrombotic obstruction was documented by coronary angiography. Multilead epicardial ECGs showed ST segment elevations of affected left ventricular (LV) areas within 2 minutes after thrombus injection, and LV segmental wall cyanosis with hypocontraction was observed within 10 minutes in the myocardial areas supplied by the thrombosed artery. Ten animals then received an initial dose of streptokinase (STK), 250,000 U (intravenous), followed by STK, 1000 to 3000 U/min (intracoronary), while nine control dogs untreated with STK received normal saline infusion. All but one STK-treated animal (all nine animals receiving intracoronary STK) had reestablishment of blood flow in the previously occluded vessels within 1 1/2 hours, disappearance of ventricular cyanosis, return of normal LV contractile function, and normalization of elevated ST segments within 1 hour after intracoronary STK therapy. In contrast, in the non-STK-treated control group, all animals had continued coronary obstruction, progressive ST elevations, and worsening LV cyanosis and hypocontraction until death or for more than 3 hours post thrombus; three control animals died of ventricular fibrillation (VF) within 1 hour of thrombus occlusion, three more died of VF within 2 hours post thrombus, and only three survived beyond 2 hours post thrombus. Postmortem examination of non-STK-treated animals revealed extensive residual coronary thrombus. All intracoronary STK-treated animals evidenced absence of residual coronary thrombus at postmortem examination. These data provide clinically relevant evidence that early intracoronary STK effects thrombolysis in AMI by reopening coronary vessels occluded by fresh thrombus, thereby protecting myocardium from further ischemia and necrosis, preserving LV function, and

  13. Deficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy

    PubMed Central

    Onclinx, Cécile; Dogne, Sophie; Jadin, Laurence; Andris, Fabienne; Grandfils, Christian; Jouret, François; Mullier, François; Flamion, Bruno

    2015-01-01

    Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are hyaluronidases 1 and 2, neither of which is active in the bloodstream. We generated hyaluronidase 2-deficient mice. These animals suffer from chronic, mild anemia and thrombocytopenia, in parallel with a 10-fold increase in plasma hyaluronan concentration. In this study we explored the mechanism of these hematologic anomalies. The decreased erythrocyte and platelet counts were attributed to peripheral consumption. The erythrocyte half-life was reduced from 25 to 8 days without signs of premature aging. Hyaluronidase 2-deficient platelets were functional. Major intrinsic defects in erythrocyte membrane or stability, as well as detrimental effects of high hyaluronan levels on erythrocytes, were ruled out in vitro. Normal erythrocytes transfused into hyaluronidase 2-deficient mice were quickly destroyed but neither splenectomy nor anti-C5 administration prevented chronic hemolysis. Schistocytes were present in blood smears from hyaluronidase 2-deficient mice at a level of 1% to 6%, while virtually absent in control mice. Hyaluronidase 2-deficient mice had increased markers of endothelial damage and microvascular fibrin deposition, without renal failure, accumulation of ultra-large multimers of von Willebrand factor, deficiency of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13 (ADAMTS13), or hypertension. There was no sign of structural damage in hepatic or splenic sinusoids, or in any other microvessels. We conclude that hyaluronidase 2 deficiency induces chronic thrombotic microangiopathy with hemolytic anemia in mice. The link between this uncommon condition and hyaluronidase 2 remains to be explored in humans. PMID:25934767

  14. The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy.

    PubMed

    Jodele, Sonata; Zhang, Kejian; Zou, Fanggeng; Laskin, Benjamin; Dandoy, Christopher E; Myers, Kasiani C; Lane, Adam; Meller, Jaroslav; Medvedovic, Mario; Chen, Jenny; Davies, Stella M

    2016-02-25

    Transplant-associated thrombotic microangiopathy (TA-TMA) occurs frequently after hematopoietic stem cell transplantation (HSCT) and can lead to significant morbidity and mortality. There are no data addressing individual susceptibility to TA-TMA. We performed a hypothesis-driven analysis of 17 candidate genes known to play a role in complement activation as part of a prospective study of TMA in HSCT recipients. We examined the functional significance of gene variants by using gene expression profiling. Among 77 patients undergoing genetic testing, 34 had TMA. Sixty-five percent of patients with TMA had genetic variants in at least one gene compared with 9% of patients without TMA (P < .0001). Gene variants were increased in patients of all races with TMA, but nonwhites had more variants than whites (2.5 [range, 0-7] vs 0 [range, 0-2]; P < .0001). Variants in ≥3 genes were identified only in nonwhites with TMA and were associated with high mortality (71%). RNA sequencing analysis of pretransplantation samples showed upregulation of multiple complement pathways in patients with TMA who had gene variants, including variants predicted as possibly benign by computer algorithm, compared with those without TMA and without gene variants. Our data reveal important differences in genetic susceptibility to HSCT-associated TMA based on recipient genotype. These data will allow prospective risk assessment and intervention to prevent TMA in highly susceptible transplant recipients. Our findings may explain, at least in part, racial disparities previously reported in transplant recipients and may guide treatment strategies to improve outcomes.

  15. Acquired Equivalence Changes Stimulus Representations

    ERIC Educational Resources Information Center

    Meeter, M.; Shohamy, D.; Myers, C. E.

    2009-01-01

    Acquired equivalence is a paradigm in which generalization is increased between two superficially dissimilar stimuli (or antecedents) that have previously been associated with similar outcomes (or consequents). Several possible mechanisms have been proposed, including changes in stimulus representations, either in the form of added associations or…

  16. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  17. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  18. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  19. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  20. Cerebral Thrombotic Complications Related to l-Asparaginase Treatment for Acute Lymphoblastic Leukemia: Retrospective Review of 10 Cases.

    PubMed

    Eden, D; Hipkins, R; Bradbury, C A

    2016-09-01

    l-Asparaginase is a potent antileukemia agent and an essential part of treatment protocols for acute lymphoblastic leukemia. However, toxicity limits dose escalation, especially in adults. This includes a significant risk of thrombosis, which remains an important source of avoidable morbidity and mortality. Here, we provide a detailed report of 10 cases of cerebral thrombotic complications that occurred over a 5-year period at 4 large tertiary referral hospitals. To our knowledge, this is the first report of this type in the published literature. PMID:25693917

  1. Ante-mortem diagnosis of pulmonary tumour thrombotic microangiopathy in a patient with unrecognised extramammary Paget's disease.

    PubMed

    Banno, Aya; Chiba, Keijiro; Kasai, Hiroko; Nagami, Keiichi

    2016-01-01

    Pulmonary tumour thrombotic microangiopathy (PTTM) resulting in fatal pulmonary hypertension is a rare complication of malignancy. Patients with PTTM generally suffer rapid deterioration of hypoxaemia, and a diagnosis is often only made at autopsy. We report a case of extramammary Paget's disease associated with PTTM. An ante-mortem diagnosis was made based on cytology of blood aspirated from a pulmonary artery catheter in a wedged position. Together with a review of the literature, this case highlights the potential diagnostic value of blood cytology in patients with cancer with rapidly progressing pulmonary hypertension. PMID:27566212

  2. Acquired Aplastic Anemia in Children

    PubMed Central

    Hartung, Helge D.; Olson, Timothy S.; Bessler, Monica

    2013-01-01

    SYNOPSIS This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder. PMID:24237973

  3. Emotional attention in acquired prosopagnosia.

    PubMed

    Peelen, Marius V; Lucas, Nadia; Mayer, Eugene; Vuilleumier, Patrik

    2009-09-01

    The present study investigated whether emotionally expressive faces guide attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia. Patient PS, a pure case of acquired prosopagnosia with intact right middle fusiform gyrus, performed two behavioral experiments and a functional imaging experiment to address these questions. In a visual search task involving face stimuli, PS was faster to select the target face when it was expressing fear or happiness as compared to when it was emotionally neutral. In a change detection task, PS detected significantly more changes when the changed face was fearful as compared to when it was neutral. Finally, an fMRI experiment showed enhanced activation to emotionally expressive faces and bodies in right fusiform gyrus. In addition, PS showed normal body-selective activation in right fusiform gyrus, partially overlapping the fusiform face area. Together these behavioral and neuroimaging results show that attention was preferentially allocated to emotional faces in patient PS, as observed in healthy subjects. We conclude that systems involved in the emotional guidance of attention by facial expression can function normally in acquired prosopagnosia, and can thus be dissociated from systems involved in face identification.

  4. Acquired causes of intestinal malabsorption.

    PubMed

    van der Heide, F

    2016-04-01

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics. PMID:27086886

  5. Relation Between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

    PubMed

    Giustino, Gennaro; Kirtane, Ajay J; Généreux, Philippe; Baber, Usman; Witzenbichler, Bernhard; Neumann, Franz-Josef; Weisz, Giora; Maehara, Akiko; Rinaldi, Michael J; Metzger, Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Brodie, Bruce R; Stuckey, Thomas D; Dangas, George D; Francese, Dominic P; Litherland, Claire; Mehran, Roxana; Stone, Gregg W

    2016-06-01

    Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation. PMID:27067621

  6. The effect of platelet autoantibodies on the course of the disease and clinical response of patients with idiopathic thrombocytopenic purpura.

    PubMed

    Sikorska, A; Konopka, L; Maślanka, K

    2008-02-01

    In this study, we evaluated the response to treatment of 409 idiopathic thrombocytopenic purpura (ITP) patients who were tested for the presence of platelet-associated autoantibodies by direct-platelet immunofluorescence test (PIFT) and for the presence of plasma antibodies directed against the GPIIb/IIIa, GPIb and GPIa/IIa by monoclonal antibody immobilization of platelet antigens (MAIPA). In patients with platelet autoantibodies in comparison with patients without antibodies more frequently were observed the chronic form of disease (83.5%vs. 68.5%) and severe symptoms of haemorrhage diathesis (17.3%vs. 6.9%). Evaluation of the treatment response (to corticosteroids, immunosuppressive drugs and splenectomy) referred to patients with complete response, e.g. complete remission defined as platelet count of >100 x 10(9)/l for at least 2 years. The percentage of complete response in the whole population of ITP patients, both with and without autoantibodies regardless of the method of treatment, was similar (about 54%). However, the presence of platelet autoantibodies had effect on patients treated with corticosteroids: complete response approximately 71% (36/51) of patients with autoantibodies and in 60% (72/120) of patients without antibodies, as well as in patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, vincristin and vinblastin); complete response approximately 51% (11/21) of patients with autoantibodies and in 34.8% (6/17) of patients without autoantibodies. The presence of autoantibodies had no effect on the response of splenectomy patients. PMID:18190469

  7. Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies.

    PubMed Central

    Dekel, B; Marcus, H; Shenkman, B; Shimoni, A; Shechter, Y; Canaan, A; Berrebi, A; Varon, D; Reisner, Y

    1998-01-01

    We have previously shown that lethally irradiated normal strains of mice, radioprotected with severe combined immunodeficient (SCID) bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC). The human/mouse radiation chimera can mount marked humoral and cellular responses to recall antigens, as well as primary responses. In the present study, we adoptively transferred splenocytes from patients with chronic immune thrombocytopenic purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone marrow. High titres of total human immunoglobulin appeared as early as 2 weeks post-transplant and declined after 6 weeks, while human anti-human platelet antibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from individual ITP patients differed in their capacity to produce either human platelet antibodies or total human immunoglobulin. Furthermore, antibodies produced in the murine system were not always identical to the original antibodies present in the serum of the patients. The study of the serological aspects of autoantibodies against human platelets in an animal model might be useful for the investigation of potential therapeutics in ITP. PMID:9767425

  8. Intracranial hemorrhage in acute and chronic childhood immune thrombocytopenic purpura over a ten-year period: an Egyptian multicenter study.

    PubMed

    Elalfy, Mohsen; Elbarbary, Nancy; Khaddah, Normine; Abdelwahab, Magy; El Rashidy, Farida; Hassab, Hoda; Al-Tonbary, Youssef

    2010-01-01

    Intracranial hemorrhage (ICH) is a rare but major cause of death in immune thrombocytopenic purpura (ITP). The authors reviewed data of 1,840 patient with ITP, from 5 pediatric hematology centers in Egypt from 1997 to 2007, to study the incidence and risk factors of ICH. Ten cases of ICH were identified with a median age at presentation of 7.5 years; 4 patients had acute ITP, 2 persistent and 4 chronic. The platelet count was <10 x 10(9)/l in 7 cases, and only 1 patient had a history of head trauma. Seven children were on treatment prior to or at the time of occurrence of ICH and all were treated by pharmacotherapy. Two children died shortly afterwards due to late referral to a specialized center. Our results suggest that treatment does not prevent ICH and that it can occur at any time during the course of the disease. Delayed referral can be considered a risk factor for unfavorable outcome of ICH, highlighting the importance of teaching sessions for patients and their parents to minimize subsequent morbidity and mortality of ICH in children with ITP. PMID:19955713

  9. Tumor necrosis factor-α -308G/A gene polymorphism in Egyptian children with immune thrombocytopenic purpura.

    PubMed

    El Sissy, Maha H; El Sissy, A H; Elanwary, Sherif

    2014-07-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the cause of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. Children with ITP have a T-helper 1-type cytokine pattern with elevated levels of tumor necrosis factor-alpha (TNF-α) as in most autoimmune diseases. Researchers have shown that polymorphism in the TNF-α gene at position -308 affects gene transcriptions with increased TNF-α production. The current case-control study aimed at detecting the frequency of TNF-α -308G/A gene polymorphism as genetic markers in Egyptian children with ITP, and to clear out their possible role in choosing the treatment protocols of therapy, using PCR restriction fragment length polymorphism assay. Ninety-two ITP patients and 100 age and sex-matched healthy controls were recruited in the study. The results obtained revealed that the frequency of TNF-α -308A/A homotype in ITP patients was significantly higher than that of the controls, and conferred almost six-fold increased risk of ITP acquisition. The polymorphic A allele frequency was significantly higher in ITP patients than in the controls, conferring almost two-fold increased ITP risk. In conclusion, our study suggests the possibility that TNF-α -308 gene polymorphism may contribute to the susceptibility of childhood ITP in Egyptian children.

  10. Acute renal failure after intravenous anti-D immune globulin in an adult with immune thrombocytopenic purpura.

    PubMed

    Chun, Nancy S; Savani, Bipin; Seder, Richard H; Taplin, Mary Ellen

    2003-12-01

    Intravenous anti-D immune globulin (anti-D IGIV) is indicated for the treatment of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis (IVH) and acute renal failure (ARF) after anti-D IGIV. We report the first adult patient with ITP who required and received dialysis after IVH and ARF complicating treatment with anti-D IGIV. Whether the transfusion of 2 units of Rh(D)-positive red cells, indicated for the resulting anemia, exacerbated the IVH and renal failure is unclear. Three weeks after the administration of anti-D IGIV (13 days after two hemodialysis treatments), the patient's renal function had returned to normal. This case highlights the infrequent but potentially serious side effects of anti-D IGIV and the need to monitor a patient's renal function closely if there is evidence of IVH after infusion of anti-D IGIV. If red cell transfusion is indicated, we recommend the use of Rh(D)-negative red cell products.

  11. Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

    PubMed

    Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

    2015-10-01

    NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. PMID:26117626

  12. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus. Relationship to antiphospholipid antibodies.

    PubMed

    Delezé, M; Oria, C V; Alarcón-Segovia, D

    1988-04-01

    Ten of 12 patients with systemic lupus erythematosus (SLE) who had hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) during their course had evidence of antiphospholipid antibodies either because they had a false positive VDRL test (8 patients), a prolonged partial thromboplastin time (5 patients), a lupus anticoagulant (3/4 patients), and/or anticardiolipin antibodies as determined by an ELISA method (7 patients). Antibodies to cardiolipin were found in very high levels (up to 38 standard deviations above the mean of normal controls) and were of both IgG and IgM isotypes. The 2 patients with SLE and Evans' syndrome who did not have evidence of antiphospholipid antibodies were studied at the onset of SLE which occurred with Evans' syndrome. Although cardiolipin is not a constituent of the cell wall of either platelets or erythrocytes, other phospholipids that cross react antigenically with cardiolipin are and can be exposed through cell damage. This could be a mechanism whereby hemolytic anemia and thrombocytopenia could occur in the same patient with SLE. Whether absorption of the antiphospholipid antibody during the acute episode of hemocytopenia could occur, and thus prevent its detection at such time, remains undetermined.

  13. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura.

    PubMed

    Peerschke, Ellinor I B; Andemariam, Biree; Yin, Wei; Bussel, James B

    2010-02-01

    The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 x 10(9)/l) (P = 0.027) and thrombocytopenia (platelet count < 100 x 10(9)/l) (P = 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes. PMID:19925495

  14. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura.

    PubMed

    Yildirim, Zühal Keskin; Büyükavci, Mustafa; Eren, Suat; Orbak, Zerrin; Sahin, Ali; Karakelleoğlu, Cahit

    2008-10-01

    Corticosteroids have been widely used in the treatment of idiopathic thrombocytopenic purpura (ITP). We evaluated the late side effects of high-dose methylprednisolone (HDMP) therapy on bone metabolism in children with ITP. Twenty-eight children with acute ITP treated with HDMP (30 mg/kg/d for 3 d then 20 mg/kg/d for 4 d) and 28 controls were enrolled in the study. Bone mineral density (BMD), urinary calcium creatinine ratio, urinary levels of deoxypyridinoline, serum levels of calcium, phosphate, parathyroid hormone, total alkaline phosphatase, and bone-specific alkaline phosphatase were measured in both groups. Magnetic resonance imaging of the femoral head was performed only in study group. The mean levels of serum phosphate, parathyroid hormone, urinary deoxypyridinoline, and calcium creatinine ratio were significantly increased in the study group. There was no significant difference between the 2 groups in terms of serum calcium, total alkaline phosphatase, bone-specific alkaline phosphatase, and BMD values. There was a statistically significant negative correlation between cumulative steroid dose and BMD values in study group (r = -0.379). Osteonecrosis was observed in 3 of 25 patients by magnetic resonance imaging. In conclusion, HDMP therapy, especially in high cumulative doses, increases the bone resorption and may cause osteonecrosis in children with ITP.

  15. Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study

    PubMed Central

    Barbaros, Umut; Aksakal, Nihat; Tukenmez, Mustafa; Agcaoglu, Orhan; Bostan, Mustafa Sami; Kilic, Berkay; Kalayci, Murat; Dinccag, Ahmet; Seven, Ridvan; Mercan, Selcuk

    2015-01-01

    AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy. PMID:26195874

  16. New approaches in tail-bleeding assay in mice: improving an important method for designing new anti-thrombotic agents.

    PubMed

    Saito, Max Seidy; Lourenço, André Luiz; Kang, Hye Chung; Rodrigues, Carlos Rangel; Cabral, Lucio Mendes; Castro, Helena Carla; Satlher, Plínio Cunha

    2016-06-01

    This report describes a modified, simple, low-cost and more sensitive method to determine bleeding patterns and haemoglobin concentration in a tail-bleeding assay using BALB/c mice and tail tip amputation. The cut tail was immersed in Drabkin's reagent to promote erythrocyte lysis and haemoglobin release, which was monitored over 30 min. The operator was blinded to individual conditions of the mice, which were treated with either saline (NaCl 0.15m), DMSO (0.5%) or clinical anti-thrombotic drugs. Our experimental protocols showed good reproducibility and repeatability of results when using Drabkin's reagent than water. Thus, the use of Drabkin's reagent offered a simple and low-cost method to observe and quantify the bleeding and rebleeding episodes. We also observed the bleeding pattern and total haemoglobin loss using untreated animals or those under anti-coagulant therapy in order to validate the new Drabkin method and thus confirm that it is a useful protocol to quantify haemoglobin concentrations in tail-bleeding assay. This modified method provided a more accurate results for bleeding patterns in mice and for identifying new anti-thrombotic drugs.

  17. Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

    PubMed Central

    Cui, Guozhen; Shan, Luchen; Guo, Lin; Chu, Ivan Keung; Li, Guohui; Quan, Quan; Zhao, Yun; Chong, Cheong Meng; Zhang, Zaijun; Yu, Pei; Hoi, Maggie Pui Man; Sun, Yewei; Wang, Yuqiang; Lee, Simon MingYuen

    2015-01-01

    Protein disulfide isomerase (PDI) family members including PDI and ERp57 emerge as novel targets for anti-thrombotic treatments, but chemical agents with selectivity remain to be explored. We previously reported a novel derivative of danshensu (DSS), known as ADTM, displayed strong cardioprotective effects against oxidative stress-induced cellular injury in vitro and acute myocardial infarct in vivo. Herein, using chemical proteomics approach, we identified ERp57 as a major target of ADTM. ADTM displayed potent inhibitory effects on the redox activity of ERp57, inhibited the adenosine diphosphate (ADP)-induced expressions of P-selectin and αIIbβ3 integrin, and disrupted the interaction between ERp57 and αIIbβ3. In addition, ADTM inhibited both arachidonic acid (AA)-induced and ADP-induced platelet aggregation in vitro. Furthermore, ADTM significantly inhibited rat platelet aggregation and thrombus formation in vivo. Taken together, ADTM represents a promising candidate for anti-thrombotic therapy targeting ERp57. PMID:26037049

  18. Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

    PubMed Central

    Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

    2015-01-01

    It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups. PMID:26508913

  19. Acquired Hearing Loss in Children.

    PubMed

    Kenna, Margaret A

    2015-12-01

    Hearing loss is the most common congenital sensory impairment. According to National Health and Nutrition Examination Survey data from 2001 to 2008, 20.3% of subjects aged greater than or equal to 12 had unilateral or bilateral hearing loss. The World Health Organization notes that, worldwide, there are 360 million people with disabling hearing loss, with 50% preventable. Although many hearing losses are acquired, many others are manifestations of preexisting conditions. The purpose of a pediatric hearing evaluation is to identify the degree and type of hearing loss and etiology and to outline a comprehensive strategy that supports language and social development and communication.

  20. The inhibition of acquired fear.

    PubMed

    Izquierdo, Iván; Cammarota, Martín; Vianna, Mónica M R; Bevilaqua, Lía R M

    2004-01-01

    A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of mental disorders, among which phobias, generalized anxiety, the posttraumatic stress disorder (PTSD) and some forms of depression. The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. Extinction was first described by Pavlov as a form of "internal inhibition" and was recommended by Freud and Ferenczi in the 1920s (who called it "habituation") as the treatment of choice for phobic disorders. It is used with success till this day, often in association with anxiolytic drugs. Extinction has since then been applied, also successfully and also often in association with anxiolytics, to the treatment of panic, generalized anxiety disorders and, more recently, PTSD. Extinction of learned fear involves gene expression, protein synthesis, N-methyl-D-aspartate (NMDA) receptors and signaling pathways in the hippocampus and the amygdala at the time of the first CS-no US association. It can be enhanced by increasing the exposure to the "no US" component at the time of behavioral testing, to the point of causing the complete uninstallment of the original fear response. Some theorists have recently proposed that reiteration of the CS alone may induce a reconsolidation of the learned behavior instead of its extinction. Reconsolidation would preserve the original memory from the labilization induced by its retrieval. If true, this would of course be disastrous for the psychotherapy of fear-motivated disorders. Here we show that neither the CS nor retrieval cause anything remotely like reconsolidation, but just extinction. In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most

  1. Malaria acquired in Haiti - 2010.

    PubMed

    2010-03-01

    On January 12, 2010, a 7.0 magnitude earthquake struck Haiti, which borders the Dominican Republic on the island of Hispaniola. The earthquake's epicenter was 10 miles west of the Haiti capital city of Port-au-Prince (estimated population: 2 million). According to the Haitian government, approximately 200,000 persons were killed, and 500,000 were left homeless. Malaria caused by Plasmodium falciparum infection is endemic in Haiti, and the principal mosquito vector is Anopheles albimanus, which frequently bites outdoors. Thus, displaced persons living outdoors or in temporary shelters and thousands of emergency responders in Haiti are at substantial risk for malaria. During January 12-February 25, CDC received reports of 11 laboratory-confirmed cases of P. falciparum malaria acquired in Haiti. Patients included seven U.S. residents who were emergency responders, three Haitian residents, and one U.S. traveler. This report summarizes the 11 cases and provides chemoprophylactic and additional preventive recommendations to minimize the risk for acquiring malaria for persons traveling to Haiti.

  2. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  3. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired. If, during the period for which income statements are required, the smaller reporting company has acquired... acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES...

  4. Lymphoma in acquired generalized lipodystrophy.

    PubMed

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.

  5. Comparison of anti-D immunoglobulin, methylprednisolone, or intravenous immunoglobulin therapy in newly diagnosed pediatric immune thrombocytopenic purpura.

    PubMed

    Celik, Muhittin; Bulbul, Ali; Aydogan, Gönül; Tugcu, Deniz; Can, Emrah; Uslu, Sinan; Dursun, Mesut

    2013-02-01

    This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count <20,000/mm(3) were prospectively randomized to treatment with anti-D Ig (50 μg/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment (P < 0.05). Chronic ITP developed in 30% of the anti-D Ig group, 35% of the methylprednisolone group, and 25% of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 μg/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment.

  6. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    SciTech Connect

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  7. Predictors of the post-thrombotic syndrome and their effect on the therapeutic management of deep vein thrombosis.

    PubMed

    Galanaud, Jean-Philippe; Monreal, Manuel; Kahn, Susan R

    2016-10-01

    The post-thrombotic syndrome (PTS), which refers to chronic clinical manifestations of venous insufficiency after a deep vein thrombosis (DVT), is a frequent occurrence. Because treatment options for PTS are limited, its management mainly relies on the prevention of its occurrence after DVT. Among identified predictors of PTS, extensive proximal location of DVT directly modifies the treatment of DVT because of the possibility of performance of complementary endovascular techniques. The association between poor international normalized ratio control and subsequent PTS should encourage physicians to perform frequent and regular international normalized ratio monitoring of patients receiving vitamin K antagonists. Other identified PTS risk factors are ipsilateral DVT recurrence, older age, pre-existing primary venous insufficiency, obesity, and residual venous obstruction, but these are less amenable to therapy. Because of their potential therapeutic implications, identification of biomarkers that are predictive of PTS such as markers of inflammation is crucial and such research is ongoing. PMID:27639012

  8. Clinical diseases with thrombotic risk and their pharmacologycal treatment: How they change the therapeutic attitude in dental treatments

    PubMed Central

    Martínez-López, Federico; Arrieta-Blanco, Juan J.; Oñate-Cabrerizo, Daniel; Cabrerizo-Merino, Maria C.

    2013-01-01

    The new antiplatelets and anticoagulant drugs have been recently introduced in the daily medical practices for the control of thromboembolism associated with different diseases. The dental assistance of these patients forces us to know these drugs, understand their action mechanisms and try to decrease the risks that entail ours actions in these patients, making a thorough analysis of the risk of bleeding that is going to be related to our medical intervention, as well as the use of all the control measures of the hemorrhage from our knowledge with these patients, and to be prudent. The communication with the medical specialist that supervises these patients must be maxim, being necessary to make clinic trials for establishing protocols or guides of the handling with these patients during the odontological treatment. Key words:Antiplatelet drugs, anticoagulants drugs, new/classic, thrombotic risk, hemorrhagic risk, dental treatment, caution. PMID:24121924

  9. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  10. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  11. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  12. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  13. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  14. High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

    PubMed

    Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

    2014-11-01

    Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

  15. Down-regulation of the serotonin transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin

    PubMed Central

    Ziu, Endrit; Mercado, Charles P.; Li, Yicong; Singh, Preeti; Ahmed, Billow A.; Freyaldenhoven, Samuel; Lensing, Shelly; Ware, Jerry; Kilic, Fusun

    2012-01-01

    An elevated plasma concentration of serotonin ([5-HT]) is a common feature of cardiovascular disease often associated with enhanced platelet activation and thrombosis. Whether elevated in vivo plasma 5-HT per se represents an independent risk factor for platelet hyperreactivity or only is an epiphenomenon of cardiovascular disease is poorly understood. We examined in vitro and in vivo platelet function following a 24 hr elevation of plasma [5-HT] in mice. In vivo administration of 5-HT using osmotic minipumps increased plasma [5-HT] in treated mice compared to control mice instrumented with saline loaded pumps. 5-HT infusion did not increase systolic blood pressure, but markers of platelet activation including P-selectin and PEJon/A staining were increased and these findings coincided with the enhanced aggregation of isolated platelets in response to type I fibrillar collagen. Tail bleeding times and the time to occlusion following chemical damage to the carotid artery were shortened in 5-HT-infused mice. 5-HT-infused mice were treated with paroxetine (Prx) to block 5-HT uptake via the serotonin transporter (SERT). Prx lowered platelet [5-HT] and attenuated platelet activation and aggregation. These results and our biochemical indices of enhanced 5-HT intracellular signaling in the platelets of 5-HT-infused mice reveal a mechanistic link between elevated plasma [5-HT], abnormal intracellular 5-HT signaling and accentuated platelet aggregation. Although a down-regulation of the serotonin transporter (SERT) on the platelet surface may counteract the pro-thrombotic influence of elevated plasma [5HT], this compensatory mechanism may fail to prevent the increased thrombotic risk caused by elevated plasma [5-HT]. PMID:22366712

  16. Statins but Not Aspirin Reduce Thrombotic Risk Assessed by Thrombin Generation in Diabetic Patients without Cardiovascular Events: The RATIONAL Trial

    PubMed Central

    Macchia, Alejandro; Laffaye, Nicolás; Comignani, Pablo D.; Cornejo Pucci, Elena; Igarzabal, Cecilia; Scazziota, Alejandra S.; Herrera, Lourdes; Mariani, Javier A.; Bragagnolo, Julio C.; Catalano, Hugo; Tognoni, Gianni; Nicolucci, Antonio

    2012-01-01

    Background The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events. Methodology/Principal Findings Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent. Conclusions/Significance While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. Trial Registration ClinicalTrials.gov NCT00793754 PMID:22470429

  17. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of liabilities, a merger or consolidation, or any similar transaction....

  18. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?

    PubMed

    Crow, Andrew R; Lazarus, Alan H

    2008-04-01

    Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article.

  19. Associative Learning Through Acquired Salience.

    PubMed

    Treviño, Mario

    2015-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction.

  20. Infections Acquired in the Garden.

    PubMed

    Cunha, Cheston B; Cunha, Burke A

    2015-10-01

    Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis. PMID:26542044

  1. Inherited or acquired metabolic disorders.

    PubMed

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series. PMID:27432685

  2. Infections Acquired in the Garden.

    PubMed

    Cunha, Cheston B; Cunha, Burke A

    2015-10-01

    Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis.

  3. Associative Learning Through Acquired Salience

    PubMed Central

    Treviño, Mario

    2016-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  4. Associative Learning Through Acquired Salience.

    PubMed

    Treviño, Mario

    2015-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  5. Clinicopathological associations of acquired erythroblastopenia

    PubMed Central

    Gunes, Gursel; Malkan, Umit Yavuz; Yasar, Hatime Arzu; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Demiroglu, Haluk; Sayinalp, Nilgun; Aksu, Salih; Etgul, Sezgin; Aslan, Tuncay; Goker, Hakan; Ozcebe, Osman Ilhami; Buyukasik, Yahya

    2015-01-01

    Introduction: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. Background: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. Material and method: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. Results: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). Discussion: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. Conclusion: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated. PMID:26885236

  6. Woman with Sickle Cell Disease with Current Sigmoid Sinus Thrombosis and History of Inadequate Warfarin Use during a Past Thrombotic Event

    PubMed Central

    Çelikbilek, Asuman; Çelikbilek, Mehmet; Bozkurt, Alper; Karakurum Göksel, Başak; Tan, Meliha; Özdoğu, Hakan

    2009-01-01

    We report a 20-year-old woman with sickle cell disease (SCD) who presented with a severe pulsating headache, nausea, and vomiting. Her history was significant for a past thrombotic event during which she had not used anticoagulation therapy as prescribed. Her mental status was mildly confused. On funduscopic examination, papilledema and retinal hemorrhages were found. Results of a computed tomogram were normal. A lumbar puncture demonstrated increased intracranial pressure (60 cm H2O). Magnetic resonance venography demonstrated a right sigmoid sinus thrombosis. Although SCD has been reported as a cause of thrombotic dural venous sinus events, this case increases the knowledge about neurological complications of SCD. The patient was treated with low molecular weight heparin, blood transfusions, acetazolamide, and methylprednisolone, and her symptoms and signs resolved. PMID:20847926

  7. Acute Cardioembolic and Thrombotic Middle Cerebral Artery Occlusions Have Different Morphological Susceptibility Signs on T2 (∗) -Weighted Magnetic Resonance Images.

    PubMed

    Zheng, Mei; Fan, Dong-Sheng

    2015-01-01

    Presence of susceptibility sign on middle cerebral artery (MCA) in T2 (∗) -weighted magnetic resonance (MR) images has been reported to detect acute MCA thromboembolic occlusion. However, the pathophysiologic course of thrombotic MCA occlusion differs from embolic occlusion, which might induce different imaging characters. Our study found that the occurrence rate of the MCA susceptibility sign in cardioembolism (CE) patients was significantly higher than in large artery atherosclerosis (LAA) patients, and the diameter of the MCA susceptibility sign for CE was greater than for LAA. Moreover, the patients with hemorrhagic transformation had MCA susceptibility signs with a significant larger mean diameter than patients without hemorrhagic transformation. Therefore, we hypothesized that the morphology of susceptibility signs could be used to differentiate acute cardioembolic and thrombotic MCA occlusions, which helped to select appropriate treatment strategies for different patients. PMID:26543869

  8. Successful Revascularization of an LCx CTO Lesion by Retrograde Approach From an Acute Thrombotic SVG Without Protection Device in an ACS Patient.

    PubMed

    Lin, Mei Mei; Wang, Ji Hung

    2016-05-25

    We describe a patient who underwent coronary artery bypass grafting (CABG) surgery with the presentation of acute coronary syndrome (ACS). The diagnostic coronary angiogram showed acute thrombotic and occluded saphenous vein graft (SVG) and proximal right coronary artery (RCA) drug eluting stent (DES) instent restenosis (ISR) with chronic total occlusion (CTO). Our strategy was to recanalize the native left circumflex coronary artery (LCx) CTO instead of SVG or RCA instent CTO. After heparinization for 5 days, the LCx antegrade approach and the retrograde approach from left anterior descending coronary artery (LAD) septal branches were first attempted but failed, and the LCx CTO was successfully revascularized retrogradely via the acute thrombotic SVG without an embolic protection device (EPD).

  9. A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection

    PubMed Central

    Rossi, Fernanda C.; Angerami, Rodrigo N.; de Paula, Erich V.; Orsi, Fernanda L.; Shang, Dezhi; del Guercio, Vânia M.; Resende, Mariângela R.; Annichino-Bizzacchi, Joyce M.; da Silva, Luiz J.; Zheng, X. Long; Castro, Vagner

    2011-01-01

    BACKGROUND Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue. PMID:19788513

  10. Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.

    PubMed

    Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi

    2011-12-01

    Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk.

  11. High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study.

    PubMed

    Veneri, Dino; Krampera, Mauro; Franchini, Massimo

    2005-03-01

    We studied the effect of Helicobacter pylori (H. pylori) eradication in 43 consecutive H. pylori-infected patients with idiopathic thrombocytopenic purpura. H. pylori was eradicated with antibiotics in 41 of them (95.3%). The difference between the mean platelet count before and after therapy was statistically significant (54.3 x 10(9)/l vs. 119.1 x 10(9)/l; P < 0.001). A sustained remission was observed in 20 patients (48.8%), after a median follow-up of 31.2 months. None of the patients still infected by H. pylori after therapy reached normal platelet values. The long-term follow-up confirms the efficacy of H. pylori eradication in H. pylori-infected ITP patients.

  12. The accuracy of platelet counting in thrombocytopenic blood samples distributed by the UK National External Quality Assessment Scheme for General Haematology.

    PubMed

    De la Salle, Barbara J; McTaggart, Paul N; Briggs, Carol; Harrison, Paul; Doré, Caroline J; Longair, Ian; Machin, Samuel J; Hyde, Keith

    2012-01-01

    A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 × 10(9)/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers. The IRM values were on average lower than the all-methods median values returned by the automated analyzers. The majority (~67%) of the automated analyzer results overestimated the platelet count compared with the IRM, with significant differences in 16.5% of cases. Performance differed between analyzer models. The observed differences may depend in part on the nature of the survey material and analyzer technology, but the findings have implications for the interpretation of platelet counts at levels of clinical decision making.

  13. The expression of IFN-gamma, IL-4, Foxp3 and perforin genes are not correlated with DNA methylation status in patients with immune thrombocytopenic purpura.

    PubMed

    Zhao, Haifeng; Du, Weiting; Wang, Donghai; Gu, Dongsheng; Xue, Feng; Ge, Jing; Sui, Tao; Yang, Renchi

    2010-01-01

    We investigated the relationship between the expression of IFN-gamma, IL-4, Foxp3 and perforin gene and the methylation status of their promoters in immune thrombocytopenic purpura (ITP) patients. Gene expression and DNA methylation were determined by quantitative PCR and bisulfite genomic sequencing, respectively. The expression of IFN-gamma was higher, while the expression of IL-4 was notably lower in ITP patients when compared with the controls. Most importantly, the Th1/Th2 (IFN-gamma/IL-4) was remarkably higher in ITP patients, showing that the ITP patients were mainly in the Th1 polarization response. Although the methylation rate of CpGs located at -409 of perforin was higher (p = 0.0376) and that of IFN-gamma were relatively higher (p = 0.0582) in ITP, we did not find the negative correlation between the expression of those genes and the methylation of their promoters. PMID:20100010

  14. Shiga toxin-2 results in renal tubular injury but not thrombotic microangiopathy in heterozygous factor H-deficient mice

    PubMed Central

    Paixão-Cavalcante, D; Botto, M; Cook, H T; Pickering, M C

    2009-01-01

    Haemolytic uraemic syndrome (HUS) is characterized by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure because of thrombotic microangiopathy (TMA). It may be caused by infection with Shiga toxin-producing enteropathic bacteria (Stx-associated HUS) or with genetic defects in complement alternative pathway (CAP) regulation (atypical HUS). We hypothesized that defective complement regulation could increase host susceptibility to Stx-associated HUS. Hence, we studied the response of mice with heterozygous deficiency of the major CAP regulator, factor H, to purified Stx-2. Stx-2 was administered together with lipopolysaccharide to wild-type and Cfh+/− C57BL/6 animals. Forty-eight hours after administration of the first Stx-2 injection all animals developed significant uraemia. Renal histology demonstrated significant tubular apoptosis in the cortical and medullary areas which did not differ between wild-type or Cfh+/− Stx-2-treated mice. Uraemia and renal tubular apoptosis did not develop in wild-type or Cfh+/− animals treated with lipopolysaccharide alone. No light microscopic evidence of TMA or abnormal glomerular C3 staining was demonstrable in the Stx-2 treated animals. In summary, Stx-2 administration did not result in TMA in either Cfh+/− or wild-type C57BL/6 mice. Furthermore, haploinsufficiency of factor H did not alter the development of Stx-2-induced renal tubular injury. PMID:19040606

  15. Fatal diffuse thrombotic microangiopathy after a bite by the "Fer-de-Lance" pit viper (Bothrops lanceolatus) of Martinique.

    PubMed

    Malbranque, Stéphane; Piercecchi-Marti, Marie Dominique; Thomas, Laurent; Barbey, Christophe; Courcier, Dominique; Bucher, Bernard; Ridarch, Alex; Smadja, Didier; Warrell, David A

    2008-06-01

    In Martinique, a man bitten two days earlier by a pit viper (Bothrops lanceolatus) was hospitalized with impaired consciousness and tetraplegia. Investigations confirmed cerebral and myocardial infarctions. Resolving thrombocytopenia was associated with virtually normal blood prothrombin time/activated partial thromboplastin time but increasing hyperfibrinogenemia. Despite specific antivenom treatment, he developed fatal left ventricular failure six days after the bite. At autopsy, multiple cerebral, myocardial and mesenteric infarctions were found. Rupture of mitral chordae tendinae was the likely cause of death. Histopathologic examination showed multi-focal thrombotic microangiopathy with intimal-medial dissection by thrombi extending from foci of endothelial damage in small cerebral, myocardial, pulmonary, mesenteric, and interlobular renal arteries and arterioles. These findings were the causes of infarctions. There was intense angiogenesis in organizing cerebral infarcts. Immunohistochemical analysis showed platelet aggregates and endothelial cells within microthrombi. Viperidae venoms contain vascular endothelial toxins, notably metalloproteinase hemorrhagins, but von Willebrand factor activators or vascular endothelial growth factor-type factors are more likely to have been implicated in this case. PMID:18541759

  16. Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT.

    PubMed

    Laskin, B L; Goebel, J; Davies, S M; Khoury, J C; Bleesing, J J; Mehta, P A; Filipovich, A H; Paff, Z N; Lawrence, J M; Yin, H J; Pinkard, S L; Jodele, S

    2011-05-01

    Patients undergoing auto-SCT for neuroblastoma present a unique population to study transplant-associated thrombotic microangiopathy (TA-TMA), due to standardized chemotherapy and later exposure to radiation and cis-retinoic acid (cis-RA). We retrospectively analyzed 20 patients after auto-SCT to evaluate early clinical indicators of TA-TMA. A total of 6 patients developing TA-TMA (30% prevalence) were compared with 14 controls. Four of six patients were diagnosed with TA-TMA by 25 days after auto-SCT. Compared with controls, TA-TMA patients had higher average systolic and diastolic blood pressure levels during high-dose chemotherapy and developed hypertension by day 13 after auto-SCT. Proteinuria was a significant marker for TA-TMA, whereas blood and platelet transfusion requirements were not. Serum creatinine did not differ between groups post transplant. However, patients with TA-TMA had a 60% decrease in renal function from baseline by nuclear glomerular filtration rate, compared with a 25% decrease in those without TA-TMA (P=0.001). There was no TA-TMA-related mortality. Significant complications included end-stage renal disease (n=1) and polyserositis (n=3). Patients with TA-TMA were unable to complete cis-RA therapy after auto-SCT. We suggest that careful attention to blood pressure and urinalysis will assist in the early diagnosis of TA-TMA, whereas serum creatinine seems to be an insensitive marker for this condition.

  17. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  18. Acquired Surface Dyslexia: The Evidence from Hebrew.

    ERIC Educational Resources Information Center

    Birnboim, Smadar

    1995-01-01

    Investigates the symptoms of acquired surface dyslexia in Hebrew. Four acquired surface dyslexic adults were compared with eight normal second graders in terms of reading strategy. Homophones and homographs were a major source of difficulty for native Hebrew surface dyslexic readers; the normal second graders used a non-lexical strategy. (45…

  19. Potential disadvantages of using socially acquired information.

    PubMed Central

    Giraldeau, Luc-Alain; Valone, Thomas J; Templeton, Jennifer J

    2002-01-01

    The acquisition and use of socially acquired information is commonly assumed to be profitable. We challenge this assumption by exploring hypothetical scenarios where the use of such information either provides no benefit or can actually be costly. First, we show that the level of incompatibility between the acquisition of personal and socially acquired information will directly affect the extent to which the use of socially acquired information can be profitable. When these two sources of information cannot be acquired simultaneously, there may be no benefit to socially acquired information. Second, we assume that a solitary individual's behavioural decisions will be based on cues revealed by its own interactions with the environment. However, in many cases, for social animals the only socially acquired information available to individuals is the behavioural actions of others that expose their decisions, rather than the cues on which these decisions were based. We argue that in such a situation the use of socially acquired information can lead to informational cascades that sometimes result in sub-optimal behaviour. From this theory of informational cascades, we predict that when erroneous cascades are costly, individuals should pay attention only to socially generated cues and not behavioural decisions. We suggest three scenarios that might be examples of informational cascades in nature. PMID:12495513

  20. Acquired Brown's syndrome: an unusual cause.

    PubMed

    Booth-Mason, S; Kyle, G M; Rossor, M; Bradbury, P

    1985-10-01

    A 62-year-old man with acquired Brown's syndrome is presented. This was due to an orbital metastatic deposit, a cause not previously reported. Other causes of this disorder and its treatment are discussed.

  1. PAI-1 over-expression decreases experimental post-thrombotic vein wall fibrosis by a non-vitronectin dependent mechanism

    PubMed Central

    Obi, Andrea T.; Diaz, Jose A.; Ballard-Lipka, Nicole L.; Roelofs, Karen J.; Farris, Diana M.; Lawrence, Daniel A.; Wakefield, Thomas W.; Henke, Peter K.

    2014-01-01

    SUMMARY Background Factors associated with post-thrombotic syndrome are known clinically, but the underlying cellular processes at the vein wall are not well-delineated. Prior work suggests that vein wall damage does not correlate with thrombus resolution, but rather with plasminogen activator-1 (PAI-1) and matrix metalloproteinase (MMP) activity. Objective We hypothesized that PAI-1 would confer post venous thrombosis (VT) vein wall protection via a Vitronectin (Vn) dependent mechanism. Methods A stasis model of VT was used with harvest over 2 weeks, in wild type (WT), Vn−/−, and PAI-1 overexpressing mice (PAI-1 Tg). Results PAI-1 Tg mice had larger VT at 6 and 14 days, compared to controls, but Vn−/−mice had no alteration of VT resolution. Gene deletion of Vn resulted in increased, rather than expected decrease in circulating PAI-1 activity. While both Vn−/− and PAI-1 Tg had attenuated intimal fibrosis, PAI-1 Tg had significantly less vein wall collagen and a compensatory increase in collagen III gene expression. Both Vn−/− and PAI-1 Tg vein wall had less monocyte chemotactic factor-1, and fewer macrophages (F4/80), with significantly less MMP-2 activity and decreased TIMP-1 antigen. Ex vivo assessment of TGFβ mediated fibrotic response showed that PAI-1 Tg vein walls had increased profibrotic gene expression (collagen I, III, MMP-2 and α-SMA) as compared with controls, opposite of the in vivo response. Conclusions The absence of Vn increases circulating PAI-1, which positively modulates vein wall fibrosis in a dose-dependent manner. Translationally, PAI-1 elevation may decrease vein wall damage after DVT, perhaps by decreasing macrophage-mediated activities. PMID:24943740

  2. Bleeding Risk during Treatment of Acute Thrombotic Events with Subcutaneous LMWH Compared to Intravenous Unfractionated Heparin; A Systematic Review

    PubMed Central

    Costantino, Giorgio; Ceriani, Elisa; Rusconi, Anna Maria; Podda, Gian Marco; Montano, Nicola; Duca, Piergiorgio; Cattaneo, Marco; Casazza, Giovanni

    2012-01-01

    Background Low Molecular Weight Heparins (LMWH) are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute coronary syndromes (ACS). Major bleeding was the primary end point. Methods Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients’ characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model. Results Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60–1.04). In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47–1.00). Conclusion The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings. PMID:22984525

  3. De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia

    PubMed Central

    Rolla, Davide; Fontana, Iris; Ravetti, Jean Louis; Marsano, Luigina; Bellino, Diego; Panaro, Laura; Ansaldo, Francesca; Mathiasen, Lisa; Storace, Giulia; Trezzi, Matteo

    2015-01-01

    Introduction: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. Conclusion: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD. PMID:26693501

  4. Anti-thrombotic and vascular effects of AR246686, a novel 5-HT2A receptor antagonist.

    PubMed

    Adams, John W; Ramirez, Juan; Ortuno, Danny; Shi, Yunqing; Thomsen, William; Richman, Jeremy G; Morgan, Michael; Dosa, Peter; Teegarden, Bradley R; Al-Shamma, Hussien; Behan, Dominic P; Connolly, Daniel T

    2008-05-31

    We have evaluated the anti-platelet and vascular pharmacology of AR246686, a novel 5-hydroxytryptamine2A (5-HT2A) receptor antagonist. AR246686 displayed high affinity binding to membranes of HEK cells stably expressing recombinant human and rat 5-HT2A receptors (Ki=0.2 nM and 0.4 nM, respectively). Functional antagonism (IC50=1.9 nM) with AR246686 was determined by inhibition of ligand-independent inositol phosphate accumulation in the 5-HT2A stable cell line. We observed 8.7-fold and 1360-fold higher affinity of AR246686 for the 5-HT2A receptor vs. 5-HT2C and 5-HT2B receptors, respectively. AR246686 inhibited 5-HT-induced amplification of ADP-stimulated human platelet aggregation (IC50=21 nM). Similar potency was observed for inhibition of 5-HT stimulated DNA synthesis in rat aortic smooth muscle cells (IC(50)=10 nM) and 5-HT-mediated contraction in rat aortic rings. Effects of AR246686 on arterial thrombosis and bleeding time were studied in a rat model of femoral artery occlusion. Oral dosing of AR246686 to rats resulted in prolongation of time to occlusion at 1 mg/kg, whereas increased bleeding time was observed at a dose of 20 mg/kg. In contrast, both bleeding time and time to occlusion were increased at the same dose (10 mg/kg) of clopidogrel. These results demonstrate that AR246686 is a high affinity 5-HT2A receptor antagonist with potent activity on platelets and vascular smooth muscle. Further, oral administration results in anti-thrombotic effects at doses that are free of significant effects on traumatic bleeding time.

  5. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft

    PubMed Central

    Terry, Christi M.; Zhuplatov, Ilya; He, Yuxia; Wun, Tze-Chein; Kim, Seong-Eun; Cheung, Alfred K.

    2015-01-01

    Background Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis. Methods A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries. Results No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft

  6. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS. PMID:26757550

  7. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.

  8. Rare manifestation of the thrombotic microangiopathy in a patient with sarcoidosis, common variable immunodeficiency and large B-cell non-hodgkin lymphoma: case report.

    PubMed

    Ekart, Robert; Grobelšek, Vesna Kovačič; Dai, Klara; Cernelč, Peter; Hojs, Radovan

    2013-06-01

    58-year old Caucasian woman was diagnosed with sarcoidosis. Low immunoglobulin levels were found and common variable immunodeficiency (CVID) was diagnosed 1year later. Laboratory tests and clinical course at this time revealed thrombotic microangiopathy (TMA). Therapeutic plasma exchange was started and her clinical status and laboratory parameters improved. According to CVID she received human immunoglobulin intravenously. Four months later we noticed swelling of the parotid glands and generalized lymphadenopathy. Histology of cervical lymph node confirmed large B-cell non-Hodgkin lymphoma (B-cell NHL). To the best of our knowledge, TMA complicating the course of sarcoidosis, CVID and B-cell NHL has never been reported. PMID:23619325

  9. Acquired cutis laxa associated with cutaneous mastocytosis.

    PubMed

    Hoang, Minh Van; Dang, Phuoc Van; Bui, Duc Van; Mejbel, Haider; Mani, Divya Thomas; Smoller, Bruce Robert; Phung, Thuy Linh

    2015-07-01

    Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be caused by genetic and metabolic disorders. It can also be acquired, possibly resulting from inflammatory processes with destruction of elastic fibers. This report describes a 26-year old woman who developed acquired cutis laxa and cutaneous mastocytosis leading to premature aging. She represents a unique co-occurrence of these two separate disease entities. To our knowledge, there has been only one published case report of acquired cutis laxa occurring in association with urticaria pigmentosa in a 4-year old girl. Our case would be a second case that exhibits the coexistence of these two disorders in an adult female. PMID:26436968

  10. Congenital and acquired bleeding disorders in infancy.

    PubMed

    Campbell, Sally Elizabeth; Bolton-Maggs, Paula H B

    2015-11-01

    The diagnosis of congenital and acquired bleeding disorders in infants requires an understanding of developmental haemostasis and the effect on laboratory testing. A systematic approach to bleeding in neonates will aid clinicians in the diagnosis and treatment, which may be caused by a wide variety of diseases. The clinical setting will help to direct the diagnostic pathway. This review will focus on the presentation and diagnosis of congenital and acquired bleeding disorders, including platelet disorders. Current research in this field is ongoing, including investigation into neonatal platelets and their different functionalities, platelet transfusion thresholds and how changes in coagulation factors may be linked to other homeostatic mechanisms.

  11. A Case Of Bilateral Acquired Localized Lipoatrophy

    PubMed Central

    Tanrıkulu, Osman; Yesilova, Yavuz; Aksoy, Mustafa

    2016-01-01

    Lipoatrophy is characterized by inflammation and tissue loss in fatty tissue. This disease may be congenital or acquired, primary or secondary. Secondary lipoatrophy develops with infections, collagen tissue diseases, tumors and drug injections. In this report, we present the case of a 14-year-old female patient who developed lipoatrophy following intramuscular steroid injection to both buttocks. PMID:27504088

  12. Mitral valve repair in acquired dextrocardia.

    PubMed

    Elmistekawy, Elsayed; Chan, Vincent; Hynes, Mark; Mesana, Thierry

    2015-10-01

    Surgical correction of valvular heart disease in patients with dextrocardia is extremely rare. We report a surgical case of mitral valve repair in a patient with acquired dextrocardia. Successful mitral valve repair was performed through a right lateral thoracotomy. We describe our surgical strategy and summarize the literature.

  13. Acquired immunodeficiency syndrome with subacute sclerosing panencephalitis.

    PubMed

    Gowda, Vykuntaraju K N; Sukanya, V; Shivananda

    2012-11-01

    A 7-year-old boy with acquired immunodeficiency syndrome, receiving antiretroviral drugs for 2 years, presented with a recent onset of myoclonic jerks and cognitive deterioration. On examination, he manifested myoclonic jerks once every 10-15 seconds. His electroencephalogram indicated periodic complexes, and his cerebrospinal fluid tested positive for measles antibodies.

  14. How Did Light Acquire a Velocity?

    ERIC Educational Resources Information Center

    Lauginie, Pierre

    2013-01-01

    We discuss how light acquired a velocity through history, from the ancient Greeks to the early modern era. Combining abstract debates, models of light, practical needs, planned research and chance, this history illustrates several key points that should be brought out in science education.

  15. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  16. Support Network Responses to Acquired Brain Injury

    ERIC Educational Resources Information Center

    Chleboun, Steffany; Hux, Karen

    2011-01-01

    Acquired brain injury (ABI) affects social relationships; however, the ways social and support networks change and evolve as a result of brain injury is not well understood. This study explored ways in which survivors of ABI and members of their support networks perceive relationship changes as recovery extends into the long-term stage. Two…

  17. Interviewing Children with Acquired Brain Injury (ABI)

    ERIC Educational Resources Information Center

    Boylan, Anne-Marie; Linden, Mark; Alderdice, Fiona

    2009-01-01

    Research into the lives of children with acquired brain injury (ABI) often neglects to incorporate children as participants, preferring to obtain the opinions of the adult carer (e.g. McKinlay et al., 2002). There has been a concerted attempt to move away from this position by those working in children's research with current etiquette…

  18. Eye Movement Correlates of Acquired Central Dyslexia

    ERIC Educational Resources Information Center

    Schattka, Kerstin I.; Radach, Ralph; Huber, Walter

    2010-01-01

    Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has…

  19. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  20. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  1. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  2. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  3. Neural Correlates of Acquired Color Category Effects

    ERIC Educational Resources Information Center

    Clifford, Alexandra; Franklin, Anna; Holmes, Amanda; Drivonikou, Vicky G.; Ozgen, Emre; Davies, Ian R. L.

    2012-01-01

    Category training can induce category effects, whereby color discrimination of stimuli spanning a newly learned category boundary is enhanced relative to equivalently spaced stimuli from within the newly learned category (e.g., categorical perception). However, the underlying mechanisms of these acquired category effects are not fully understood.…

  4. ABO blood group but not haemostasis genetic polymorphisms significantly influence thrombotic risk: a study of 180 homozygotes for the Factor V Leiden mutation.

    PubMed

    2006-12-01

    Limited data exist on the impact of additional genetic risk factors on the clinical manifestations of factor (F) V Leiden homozygotes. A retrospective multi-centre cohort study was performed to assess the role of the FII G20210A gene mutation, the protein C (PC) promoter CG haplotype, the combination of two PC polymorphisms (A-1641G, C-1654T), the FXIII Val34Leu polymorphism, two thrombin-activatable fibrinolysis inhibitor polymorphisms (Thr325Ile, Ala147Thr), two plasminogen activator inhibitor-1 polymorphisms (-675 4G/5G, A-844G), the methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism and the ABO blood group on the thrombotic phenotype in FV Leiden homozygotes. 127 subjects with venous thrombosis and 53 asymptomatic subjects were analysed. The T allele of MTHFR C677T was more frequent in symptomatic subjects than in asymptomatic ones (68% vs. 45%, P = 0.02; odds ratio (OR) 2.8, 95% CI 1.3-5.8, after adjustment for potential confounders). For the other polymorphisms, no difference was observed between symptomatic and asymptomatic subjects. The non-O blood group was more frequent among symptomatic carriers (84% vs. 57%, P = 0.0002; OR 4.1, 95% CI 1.7-9.7). In conclusion, except for the ABO blood group, none of the polymorphisms studied contribute strongly to the thrombotic risk in FV Leiden homozygotes.

  5. Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura. Danish I.T.P. Study Group.

    PubMed

    Rosthøj, S; Nielsen, S; Pedersen, F K

    1996-08-01

    Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 x 10(9)l-1, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions 1 g kg-1 (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30 mg kg-1 (n = 20) on two consecutive days. After 72 h, IVIG had induced greater platelet responses (mean PC 188 x 10(9) versus 77 x 10(9)l-1, 2p < 0.001) and raised the PC to a haemostatically safe level above 50 x 10(9)l-1 more frequently (91 versus 50%, one-sided exact p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 x 10(9)l-1 had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP. PMID:8863869

  6. Anti-platelet antibodies associated with the Canale–Smith syndrome bind to the same platelet glycoprotein complexes as those of idiopathic thrombocytopenic purpura patients

    PubMed Central

    GRODZICKY, T; BUSSEL, J B; ELKON, K B

    2002-01-01

    The Canale–Smith syndrome (CSS) is an inherited disease characterized by massive lymphadenopathy, hepatosplenomegaly and systemic autoimmunity to erythrocytes and platelets. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which approximately 60–80% of patients have anti-platelet antibodies directed against specific platelet glycoprotein complexes (GPCs) located on their membrane: GP IIb/IIIa, GPIb/IX, and GPIa/IIa. Almost all (95–100%) of the antibody-positive patients have antibodies directed against GPIIb/IIIa alone, or in combination with other glycoprotein targets. Our objective was to determine the specificities of the anti-platelet antibodies in CSS patients. The detection of anti-platelet antibodies was performed using a commercially available ELISA, the Pak-AUTO (GTI, Brookfield, WI), in which highly purified GPIIb/IIIa, GPIb/IX, and GPIa/IIa are immobilized on microtitre plates, incubated with serum or plasma, and subsequently developed with an antihuman polyclonal immunoglobulin. Of 14 CSS patients tested, 11 (79%) had anti-platelet antibodies in their serum directed toward at least one of the three major GPC, nine (82%) of which were against GPIIb/IIIa alone or in combination. Antibodies detected in the sera of ITP patients had similar specificities. No such antibodies were detected in samples from 25 consecutive normal controls. These results demonstrate that a genetically defined defect in lymphocyte apoptosis results in a humoral autoimmune response with anti-platelet specificities very similar to the common idiopathic form of autoimmune thrombocytopenia. PMID:11876752

  7. DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.

    PubMed

    Khorshied, Mervat Mamdooh; El-Ghamrawy, Mona Kamal

    2012-12-10

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

  8. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.

    PubMed

    Kane, Ian; Ragucci, Dominic; Shatat, Ibrahim F; Bussel, James; Kalpatthi, Ram

    2010-04-01

    This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 microg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high-dose anti-D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti-D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti-D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high-dose anti-D are effective first-line therapies for childhood ITP. However, we observed increased ADRs in the high-dose anti-D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high-dose anti-D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.

  9. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.

    PubMed

    Gaines, Ann Reed

    2005-09-01

    The Food and Drug Administration (FDA) licensed Rh(o)(D) immune globulin intravenous (anti-D IGIV) on March 24, 1995, for treatment of immune thrombocytopenic purpura (ITP). A previous review described data on 15 patients who experienced acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP or secondary thrombocytopenia. Eleven of those patients also experienced clinically compromising anemia, transfusion with packed red blood cells, renal insufficiency, dialysis, or death. That review suggested that patients receiving anti-D IGIV be monitored for those and other potential complications of hemoglobinemia, particularly disseminated intravascular coagulation (DIC). Through November 30, 2004, the FDA received 6 reports of DIC associated with "acute hemolysis" (or similar terms), 5 of which involved fatalities. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death. This review presents the first case series of DIC associated with acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP. The purpose of this review is to increase awareness among physicians and other health care professionals that DIC may be a rare but potentially severe complication of anti-D IGIV treatment. Increased awareness of DIC as a diagnostic possibility may enable prompt recognition and medical intervention in affected patients.

  10. Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children.

    PubMed

    Freiberg, A; Mauger, D

    1998-01-01

    We analyzed data from 20 children treated for acute or chronic idiopathic (immune) thrombocytopenic purpura (ITP) at a single institution to determine the relationship between dose of intravenous anti-D immune globulin (WinRho SDF; Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in the therapy of ITP. Higher doses of anti-D were clearly associated with a greater therapeutic response in the platelet count, with no increase in hemolysis for both acute and chronic ITP. A significant correlation was found between dose and peak increase in platelet count measured in the 14 days following administration. This effect was present for both acute ITP (17 infusions, P = .0001) and chronic ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the decrease in hemoglobin was greater than 2.5 for only three infusions, and the largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic anemia. Furthermore, for both acute and chronic ITP there was no relationship between the decrease in hemoglobin and the dose given (P = .22), nor between the increase in platelet count and fall in hemoglobin (P = .27). This analysis supports the use of higher doses of anti-D for the treatment of ITP, and demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute and chronic ITP.

  11. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles.

    PubMed

    Emilia, Giovanni; Luppi, Mario; Zucchini, Patrizia; Morselli, Monica; Potenza, Leonardo; Forghieri, Fabio; Volzone, Francesco; Jovic, Gordana; Leonardi, Giovanna; Donelli, Amedea; Torelli, Giuseppe

    2007-12-01

    Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis. PMID:17652264

  12. Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults

    SciTech Connect

    Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

    1987-01-01

    Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

  13. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ

    SciTech Connect

    Heyns A du, P.; Badenhorst, P.N.; Loetter, M.G.P.; Pieters, H.; Wessels, P.; Kotze, H.F.

    1986-01-01

    Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr-labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

  14. Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura

    SciTech Connect

    Gangarossa, S.; Mattina, T.; Romano, V.; Milana, G.; Mollica, F.; Schiliro, G.

    1996-03-15

    Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. 23 refs., 2 figs., 1 tab.

  15. Targeting reservoirs to control human infections – a one health approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shiga toxin producing Escherichia coli (STEC) cause hemorrhagic colitis and potentially fatal extraintestinal sequelae, such as the hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, in humans. Currently, treatment of human STEC disease is only symptomatic and supportive. Antibioti...

  16. Haematology and neurology

    PubMed Central

    Austin, Steven; Cohen, Hannah; Losseff, Nick

    2007-01-01

    This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed. PMID:17369588

  17. Bruising and Bleeding

    MedlinePlus

    ... or purple dots (petechiae), red or purple patches (purpura), bruises (ecchymoses), or small blood vessels that are ... syndrome HIV infection Immune thrombocytopenia Leukemia Thrombotic thrombocytopenic purpura Increased number of platelets (which often causes excessive ...

  18. How Is Immune Thrombocytopenia Treated?

    MedlinePlus

    ... Blood Transfusion Bone Marrow Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... who have bleeding symptoms, other than merely bruising (purpura), usually are treated. Children who have mild ITP ...

  19. Inherited, congenital and acquired disorders by hemostasis (vascular, platelet & plasmatic phases) with repercussions in the therapeutic oral sphere

    PubMed Central

    Arrieta-Blanco, Juan J.; Martínez-López, Federico; Oñate-Cabrerizo, Daniel; Cabrerizo-Merino, Maria C.

    2014-01-01

    The hemostasis alterations, either congenital or hereditary origin, and acquired, are circumstances that hinder oral care to patients who suffer them and also generates in the professional who has to attend, high stress. Bleeding control once established and dental treatment planning, both in the aspect of preparation, as the realization of the odonto-stomatological therapeutic, has suffered updates that do need to remember certain aspects of the care of these patients. But we must not forget that the hematologist or internist who controls the patient’s medical condition, is a cornerstone for the planning and implementation of treatment plans. We must also remember that, in certain circumstances, treatment should be performed in a hospital setting. In this review, we aim to provide the odonto-stomatologist guidance on how to address the problem and provide simple and updated guidelines to apply in the treatment of these people. Key words:Hemostasis disorder, oral care protocols, haemorrhagic and thrombotic disorders, haemophilia, von willebrand disease, desmopressin, purple, thrombocytopenia, thrombocytopathies. PMID:24121923

  20. Acquired undescended testis: putting the pieces together.

    PubMed

    Hack, W W M; Goede, J; van der Voort-Doedens, L M; Meijer, R W

    2012-02-01

    Acquired undescended testis is now a well-recognized disorder. It is seen in 1.5% of pre-pubertal boys and accounts for the 1-2% orchidopexy rate in older boys. Its pathogenesis remains largely unclear, but it may be caused by a fibrous remnant of the processus vaginalis. There is much controversy over its management, and the proper management awaits a randomized-controlled trial. Until now, follow-up data are available only for cases of spontaneous descent or pubertal orchidopexy. It is speculated that acquired undescended testis is in fact congenital and because of a short funiculus at birth, allowing a low-scrotal position early in life. However, as the boy grows, the testis might evolve into an undescended state. When testosterone surges at puberty, spontaneous descent occurs in three of every four cases.

  1. Clinical laboratory data: acquire, analyze, communicate, liberate.

    PubMed

    Azzazy, Hassan M E; Elbehery, Ali H A

    2015-01-01

    The availability of portable healthcare devices, which can acquire and transmit medical data to remote experts would dramatically affect healthcare in areas with poor infrastructure. Smartphones, which feature touchscreen computer capabilities and sophisticated cameras, have become widely available with over billion units shipped in 2013. In the clinical laboratory, smartphones have recently brought the capabilities of key instruments such as spectrophotometers, fluorescence analyzers and microscopes into the palm of the hand. Several research groups have developed sensitive and low-cost smartphone-based diagnostic assay prototypes for testing cholesterol, albumin, vitamin D, tumor markers, and the detection of infectious agents. This review covers the use of smartphones to acquire, analyze, communicate, and liberate clinical laboratory data. Smartphones promise to dramatically improve the quality and quantity of healthcare offered in resource-limited areas.

  2. Acquired Cystic Fibrosis Transmembrane Conductance Regulator Deficiency.

    PubMed

    Cho, Do-Yeon; Woodworth, Bradford A

    2016-01-01

    In the genetic airway disease cystic fibrosis (CF), deficiency or dysfunction of the cystic fibrosis membrane conductance regulator (CFTR) alters anion transport in respiratory epithelium and consequently disrupts mucociliary clearance. An enriched understanding of the role of CFTR in the maintenance of normal epithelial function has revealed that mild and variable CFTR mutations play a causative role in a number of diseases not classically associated with CF. Furthermore, recent evidence indicates that acquired defects in wild-type CFTR protein processing, endocytic recycling and function can contribute to the pathogenesis of airway diseases, such as chronic obstructive pulmonary disease. In this chapter, we discuss emerging findings implicating acquired CFTR dysfunction in the pathogenesis of chronic rhinosinusitis and propose a new and leading edge approach to future CRS therapy using CFTR potentiators. PMID:27466849

  3. Acquired portosystemic collaterals: anatomy and imaging*

    PubMed Central

    Leite, Andréa Farias de Melo; Mota Jr., Américo; Chagas-Neto, Francisco Abaeté; Teixeira, Sara Reis; Elias Junior, Jorge; Muglia, Valdair Francisco

    2016-01-01

    Portosystemic shunts are enlarged vessels that form collateral pathological pathways between the splanchnic circulation and the systemic circulation. Although their causes are multifactorial, portosystemic shunts all have one mechanism in common-increased portal venous pressure, which diverts the blood flow from the gastrointestinal tract to the systemic circulation. Congenital and acquired collateral pathways have both been described in the literature. The aim of this pictorial essay was to discuss the distinct anatomic and imaging features of portosystemic shunts, as well as to provide a robust method of differentiating between acquired portosystemic shunts and similar pathologies, through the use of illustrations and schematic drawings. Imaging of portosystemic shunts provides subclinical markers of increased portal venous pressure. Therefore, radiologists play a crucial role in the identification of portosystemic shunts. Early detection of portosystemic shunts can allow ample time to perform endovascular shunt operations, which can relieve portal hypertension and prevent acute or chronic complications in at-risk patient populations. PMID:27777479

  4. [Acquired renal cysts in maintenance dialysis patients].

    PubMed

    Lie, B; Hust, W; Asgarzadeh, A; Mann, H

    1986-03-01

    Ultrasonographic examination of the kidneys of 111 patients on long term maintenance hemodialysis was performed. None of the patients had genuine polycystic kidney disease. In many patients acquired cysts were found. Frequency and volume of these cysts were the same on the right and left side. There was no correlation between the age of the patients and the number of cysts. There were no differences concerning sex and type of primary renal disease. There was a significant positive correlation between time on maintenance hemodialysis and number of cysts but no correlation between number of cysts and hemoglobin concentration. This is in contrast to data in the literature. Clinical relevance of acquired kidney cysts in dialysis patients concerns hematuria, retroperitoneal bleeding, kidney stone formation, septicemia and malignancy.

  5. System Acquires Data On Reactivities Of Foams

    NASA Technical Reports Server (NTRS)

    Walls, Joe T.

    1994-01-01

    Data-acquisition and -plotting system, called DAPS(TM), developed enabling accurate and objective determination of physical properties related to reactivities of polyurethane and polyisocyanurate foams. Automated, computer-controlled test apparatus that acquires data on rates of rise, rise profiles, exothermic temperatures, and internal pressures of foams prepared from both manual and machine-mixed batches. Data used to determine minute differences between reaction kinetics and exothermic profiles of foam formulations, properties of end products which are statistically undifferentiated.

  6. Management options of acquired punctal stenosis.

    PubMed

    Bukhari, Amal A

    2013-08-01

    Punctal stenosis is a frequent source of patients referral to the otoplasty clinic and the search for a procedure that can permanently eliminate epiphora without disturbing the normal lacrimal system anatomy and physiology started centuries ago and continues today. The following article summarizes the reported procedures in the English literature in the acquired punctal stenosis with a description of techniques, success rates, and potential complications with the goal of identifying the most effective treatment strategy based on the current knowledge available.

  7. Earth Knowledge Acquired by Middle School Students

    NASA Technical Reports Server (NTRS)

    Ride, Sally

    2008-01-01

    Earth Knowledge Acquired by Middle School Students (EarthKAM), an education activity, allows middle school students to program a digital camera on board the International Space Station to photograph a variety of geographical targets for study in the classroom. Photos are made available on the web for viewing and study by participating schools around the world. Educators use the images for projects involving Earth Science, geography, physics, and social science.

  8. Acquired protein energy malnutrition in glutaric acidemia.

    PubMed

    Ma, Liqiao; Savory, Stephanie; Agim, Nnenna G

    2013-01-01

    We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica.

  9. Acquired protein energy malnutrition in glutaric acidemia.

    PubMed

    Ma, Liqiao; Savory, Stephanie; Agim, Nnenna G

    2013-01-01

    We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica. PMID:23330977

  10. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  11. The pathophysiology of acquired premature ejaculation.

    PubMed

    McMahon, Chris G; Jannini, Emmanuele A; Serefoglu, Ege C; Hellstrom, Wayne J G

    2016-08-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  12. The pathophysiology of acquired premature ejaculation

    PubMed Central

    Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J. G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  13. The pathophysiology of acquired premature ejaculation

    PubMed Central

    Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J. G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE.

  14. Computed tomographic observations pertinent to intracranial venous thrombotic and occulsive disease in childhood: state of the art, some new data, and hypotheses

    SciTech Connect

    Segall, H.D.; Ahmadi, J.; McComb, J.G.; Zee, C.S.; Becker, T.S.; Han, J.S.

    1982-05-01

    Selected topics are discussed and new observations recorded regarding computed tomographic (CT) evaluation of intracranial venous thrombotic and occlusive disease in childhood. High density of the vein of Galen and adjacent venous sinuses (relative to brain) can be seen normally in children. A number of potential pitfalls in the diagnosis of superior sagittal sinus thrombosis are also disclosed. A case of cavernous sinus thrombosis with abnormal CT changes is included. In addition, the normal CT appearance of the cavernous sinus is described. In some cases, filling defects occur which appear to correlate with normal cranial nerves. An unusual case of venous sinus occlusion by neoplasm (sarcoma) is presented. Finally, new findings in the Sturge-Weber syndrome are analyzed. Enhancement of the brain in this condition may have its basis in altered circulation resulting from fundamental venous abnormalities.

  15. The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis

    PubMed Central

    Carter, Corey A.; Browning, Robert; Oronsky, Bryan T.; Scicinski, Jan J.; Brzezniak, Christina

    2016-01-01

    A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome. PMID:26933422

  16. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  17. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  18. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients.

    PubMed

    Gaines, A R

    2000-04-15

    Rh(o)(D) immune globulin intravenous (anti-D IGIV) was licensed by the United States Food and Drug Administration (FDA) in March 1995 to treat patients with immune thrombocytopenic purpura (ITP). Anti-D IGIV induces extravascular hemolysis, an expected adverse reaction that is consistent with the presumed mechanism of action. Between licensure and April 1999, the FDA received 15 reports of hemoglobinemia and/or hemoglobinuria following anti-D IGIV administration that met the case definition for this review. The mechanism responsible for hemoglobinemia and/or hemoglobinuria is unexplained. Review of these reports was prompted by the seriousness and the unexpectedness of treatment-associated sequelae experienced by 11 patients. Of these patients, 7 developed sufficient onset or exacerbation of anemia that orders were written for packed red blood cell transfusions, although only 6 patients were transfused. Eight patients experienced the onset or exacerbation of renal insufficiency, and 2 patients underwent dialysis. One patient died due to complications of exacerbated anemia. Six patients experienced 2 to 3 sequelae. Absent validated incidence data, a 1.5% estimated incidence rate from published clinical trial data and a 0.1% estimated reporting rate from FDA and drug utilization data were calculated for reported cases of hemoglobinemia and/or hemoglobinuria. This review presents the first case series of anti-D-IGIV-associated hemoglobinemia and/or hemoglobinuria and provides pretreatment and posttreatment clinical and laboratory findings of the case series patients. The primary purpose of this review is to increase awareness of this potentially serious occurrence among physicians and health care professionals who manage ITP patients treated with anti-D IGIV, thereby enabling prompt recognition and treatment of sequelae. (Blood. 2000;95:2523-2529)

  19. The Relationship between Self-esteem and Quality of Life of Patients with Idiopathic Thrombocytopenic Purpura at Isfahan's Sayed Al-Shohada Hospital, Iran, in 2013

    PubMed Central

    Hemati, Zeinab; Kiani, Davood

    2016-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a chronic disease which is accompanied with hopelessness and loss of the sense of well-being due to its symptoms and treatment. It also affects patients' sense of social and spiritual well-being. This disorder decreases patients' self-esteem and their quality of life by changing their mental image and self-confidence. This study was performed to find the relationship between self-esteem and quality of life of patients with ITP. Subjects and Methods: This was a descriptive-analytical study on 64 patients with ITP who referred to Isfahan's Sayed Al-Shohada Hospital, Iran. In this study, patients with ITP were selected randomly using a random number chart. The data collection tools consisted of the World Health Organization Quality of Life (WHOQOL)-BREF and Coopersmith Self-esteem Inventory (CSEI). Data were analyzed using SPSS and chi-square and Mann-Whitney tests and the Pearson and Spearman’s rank correlation coefficients. Results: In total, 64 patients completed the questionnaires. Results showed that 32% of subjects were over 36 years of age and 59% were women. In addition, 29.7% of ITP patients had low self-esteem and quality of life. Chi-square test showed a significant relationship between self-esteem and quality of life of patients with ITP. Conclusions: The results of the present study showed that considerable attention must be paid to self-esteem, as one of the most important factors influencing the promotion of quality of life. Therefore, it is suggested that patient’s self-esteem be improved by the implementation of educational and psychological programs in order to decrease the consequences of poor quality of life. PMID:27252807

  20. Women and the Acquired Immunodeficiency Syndrome

    PubMed Central

    Wofsy, Constance B.

    1988-01-01

    SPECIAL EDITOR'S NOTE: Constance B. Wofsy, MD, is Co-Director of AIDS Activities at San Francisco General Hospital and Medical Center, as well as Associate Clinical Professor of Medicine at the University of California, San Francisco; Assistant Chief, Infectious Diseases, San Francisco General Hospital; and Principal Investigator, Project AWARE (Association for Women's AIDS Research and Education). Although she was not able to contribute an article for WOMEN AND MEDICINE on this very important subject, she kindly agreed to an interview. Both physicians and nonphysicians were asked what questions they had about the acquired immunodeficiency syndrome (AIDS) and the human immunodeficiency virus (HIV) in women. Images PMID:3250110

  1. Acquired plate-like osteoma cutis.

    PubMed

    Vashi, Neelam; Chu, Julie; Patel, Rishi

    2011-10-15

    Plate-like osteoma cutis is a rare disorder that has been historically classified as a congenital syndrome. It has a possible relationship to a mutation in the gene (GNAS1) that encodes the α-subunit of the stimulatory G protein, which regulates adenyl cyclase activity. We report a case of extensive plaque-like masses on the scalp and face with no abnormalities in calcium or phosphate metabolism and no preceding inflammatory cutaneous conditions. With less than ten reported cases, to our knowledge, this is one the few cases of acquired plate-like osteoma cutis described in the literature.

  2. Psychological issues in acquired facial trauma

    PubMed Central

    De Sousa, Avinash

    2010-01-01

    The face is a vital component of one’s personality and body image. There are a vast number of variables that influence recovery and rehabilitation from acquired facial trauma many of which are psychological in nature. The present paper presents the various psychological issues one comes across in facial trauma patients. These may range from body image issues to post-traumatic stress disorder symptoms accompanied by anxiety and depression. Issues related to facial and body image affecting social life and general quality of life are vital and the plastic surgeon should be aware of such issues and competent to deal with them in patients and families. PMID:21217982

  3. Triple arthrodesis for adult acquired flatfoot.

    PubMed

    Catanzariti, Alan R; Dix, Brian T; Richardson, Phillip E; Mendicino, Robert W

    2014-07-01

    The primary goal of triple arthrodesis for stage III and IV adult acquired flatfoot is to obtain a well-aligned plantigrade foot that will support the ankle in optimal alignment. Ancillary procedures including posterior muscle group lengthening, medial displacement calcaneal osteotomy, medial column stabilization, peroneus brevis tenotomy, or transfer and harvest of regional bone graft are often necessary to achieve adequate realignment. Image intensification is helpful in confirming optimal realignment before fixation. Results of triple arthrodesis are enhanced with adequate preparation of joint surfaces, bone graft/orthobiologics, 2-point fixation of all 3 tritarsal joints, and a vertical heel position.

  4. Acquired progressive lymphangioma of the nipple

    PubMed Central

    Alkhalili, Eyas; Ayoubieh, Houriya; O'Brien, William; Billings, Steven D

    2014-01-01

    A 47-year-old woman presented with left nipple itch and discomfort. On physical examination she was found to have a 7 mm lesion. She underwent bilateral mammography and bilateral breast ultrasound which were normal. A punch biopsy of the lesion was performed in the office and the specimen submitted to pathology. Histopathological examination showed ectatic vascular spaces lined by flattened, cytologically bland endothelial cells dissecting the dermal collagen. Evident lymphatic valves were present within the vascular spaces confirming that the vessels were lymphatic in nature. The diagnosis of acquired progressive lymphangioma (benign lymphangioendothelioma) was rendered. PMID:25246470

  5. Acquired scalp alopecia. Part II: A review.

    PubMed

    Sullivan, J R; Kossard, S

    1999-05-01

    The neutrophil-associated and infiltrative scarring alopecias are reviewed including folliculitis decalvans, tufted folliculitis, dissecting cellulitis of the scalp, acne keloidalis and follicular degeneration syndrome. The management of acquired scalp alopecia is also reviewed including newer, promising therapies. More specific agents targeting components of the androgen system will make the treatment of androgenetic alopecia more rewarding. Similarly new immunomodulatory therapies show great promise for the lymphocyte-associated alopecias and include a new generation of macrolide immunosuppressives (tacrolimus, SDZ ASM 981, and SDZ 281-240), some of which appear to have good transcutaneous absorption. PMID:10333615

  6. Origins of species: acquired genomes and individuality

    NASA Technical Reports Server (NTRS)

    Margulis, L.

    1993-01-01

    Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin ("Symbionticism", see p. 181, this issue).

  7. Origins of species: acquired genomes and individuality.

    PubMed

    Margulis, L

    1993-01-01

    Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin ("Symbionticism", see p. 181, this issue).

  8. AGU acquires Springer-Verlag Series

    NASA Astrophysics Data System (ADS)

    AGU has acquired Springer-Verlag's (New York) Coastal and Estuarine Studies book series. This acquisition adds thirty-nine volumes to AGU's own Coastal and Estuarine Sciences book series.Coastal and estuarine science is a rapidly growing area of research driven in part by an increasing awareness of man's impact on the coastal zone, and the importance in understanding its delicate ecosystems. This area of study enhances AGU's initiatives in interdisciplinary research. Particular emphasis is being placed on understanding the complex interactions between the physical, geological, chemical, and biological aspects of marine science.

  9. Acquired Congenital Malalignment of the Great Toenails

    PubMed Central

    Decker, Ashley; Scher, Richard K.; Avarbock, Andrew

    2016-01-01

    Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597

  10. [Acquired cystic renal disease. Association with hypernephroma].

    PubMed

    Comesaña, E; Pesqueira, D; Tardáguila, F; De la Fuente, A; Antón, I; Vidal, L; Zungri, E

    1992-02-01

    Emergence of multiple bilateral renal cysts observed in patients undergoing periodic haemodialysis is 40%. The pathology, known as Acquired Cystic Renal Disease (A.C.R.D.) presents a high association to renal cancer. Two cases of A.C.R.D. and their association with hypernephroma, one resulting in secondary retroperitoneal haemorrhage and the other in intracystic haemorrhage, are presented. Forms and diagnosis are analyzed, insisting upon the need of monitoring the patients in haemodialysis from the point of view of tumour emergence.

  11. Influence of the JAK2 V617F Mutation and Inherited Thrombophilia on the Thrombotic Risk among Patients with Myeloproliferative Disorders

    PubMed Central

    TEVET, Mihaela; IONESCU, Razvan; DRAGAN, Cornel; LUPU, Anca Roxana

    2015-01-01

    Background: A number of studies showed that the JAK2 V617F mutation increases the thrombotic risk in patients with myeloproliferative disorders (MPN) while others did not reveal this correlation, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. Our aim was to clarify the contribution of JAK2 V617F to a hypercoagulable state, as well as its interaction with other thrombophilic factors in patients with thrombosis and myeloproliferative disorders. Method: We studied 192 patients with myeloproliferative disorders, 90 with Essential thrombocytemia (ET), 42 with Polycythemia vera (PV) and 60 with Primary or idiopathic myelofibrosis (PMI). From these patients a subgroup of only 62 patients underwent laboratory screening for thrombophilia. Results: The JAK2 V617F mutation was present in 62.8% patients with myeloproliferative disorders, 97.6% with PV, 54.5 % with ET and 53.44% patients with PMI. The mutated patients had a relative risk (RR) for thrombosis at any time of 2.94 in comparison with "wild-type" patients which was 0.93; in those patients having both the mutation and thrombophilia the RR was 3.56 (95% CI 2.41-7.34) compared to patients with neither the mutation nor thrombophilia, suggesting an additive interaction between the two risk factors. Conclusion: In patients with myeloproliferatives neoplasias, the thrombotic risk is higher in the JAK2 V617F-mutated subgroup and it is further increased by the presence of inherited thrombophilia (especially by the presence of mutated F V Leiden and lupus anticoagulant). PMID:26225146

  12. Asian elephants acquire inaccessible food by blowing.

    PubMed

    Mizuno, Kaori; Irie, Naoko; Hiraiwa-Hasegawa, Mariko; Kutsukake, Nobuyuki

    2016-01-01

    Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication.

  13. Asian elephants acquire inaccessible food by blowing.

    PubMed

    Mizuno, Kaori; Irie, Naoko; Hiraiwa-Hasegawa, Mariko; Kutsukake, Nobuyuki

    2016-01-01

    Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication. PMID:26541597

  14. Eye movement correlates of acquired central dyslexia.

    PubMed

    Schattka, Kerstin I; Radach, Ralph; Huber, Walter

    2010-08-01

    Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has been no research attempting to analyze both word-based viewing time measures and local fixation patterns in dyslexic readers. The goal of the study was to find out whether specific eye movement parameters reflect pathologically preferred segmental reading in contrast to lexical reading. We compared oral reading of single words of normal controls (n=11) with six aphasic participants (two cases of deep, surface and residual dyslexia each). Participants were asked to read aloud lines of target words differing in length and frequency. Segmental reading was characterized by deviant spatial distribution of saccadic landing positions with initial fixations located mainly at the beginning of the word, while lexical readers showed the normative 'preferred landing positions' left to the center of the words. Contrary to expectation, word length did not distinguish between segmental and lexical readers, while word frequency showed the expected effect for lexical readers only. Their mean fixation duration was already prolonged during first pass reading reflecting their attempts of immediate access to lexical information. After first pass reading, re-reading time was significantly increased in all participants with acquired central dyslexia due to their exceedingly higher monitoring demands for oral reading.

  15. Acquiring functional object knowledge through motor imagery?

    PubMed

    Paulus, Markus; van Elk, Michiel; Bekkering, Harold

    2012-04-01

    A widely investigated question in the research on the acquisition of novel functional object representations is the role of the action system. Whereas most studies so far have investigated the role of active action training on the acquisition of object representation, we investigated whether people are able to acquire object representations by just imagining the use of novel objects, given that previous findings suggested that executed and imagined actions share a common representational format. To this end, participants trained the use of novel objects in a motor imagery condition. Training comprised the particular grip applied to the objects and the objects' typical end location. Subsequently, participants' object representations were assessed by means of an object detection task. The results show that participants responded slower when the novel objects were presented at functionally incorrect end locations, indicating that the participants had acquired functional knowledge about object use. Yet, there was no effect of correct versus incorrect grip. Altogether, the findings suggest that motor imagery can facilitate the acquisition of novel object representations, but point also to differences between first-hand action training and training by imagery.

  16. The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.

    PubMed

    Nieto, Maria; Calvo, Gonzalo; Hudson, Ian; Feldschreiber, Peter; Brown, David; Lee, Ching Cheng; Lay, Geoffrey; Valeri, Anna; Abadie, Eric; Thomas, Angela; Pignatti, Francesco

    2011-09-01

    On 11(th) March 2010, the European Commission issued a marketing authorization valid throughout the European Union for Revolade for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Revolade is an orphan medicinal product indicated for splenectomized patients with immune (idiopathic) thrombocytopenic purpura who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for non-splenectomized patients where surgery is contraindicated. The active substance of Revolade is eltrombopag (ATC code B02BX05). Eltrombopag increases platelet production through activation of the thrombopoietin receptor. The recommended oral dose is 50 mg once daily to achieve and maintain a platelet count of the 50×10(9)/L or more necessary to reduce or prevent the risk of bleeding. The benefit of Revolade is a durable response in maintaining platelet levels. The most common side effects include headache, nausea, hepatobiliary toxicity, diarrhea, fatigue, paresthesia, constipation, rash, pruritus, cataract, arthralgia and myalgia. The decision to grant the marketing authorization was based on the favorable recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency. The objective of this paper is to describe the data submitted to the European Medicines Agency and to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (www.ema.europa.eu). PMID:21712542

  17. Transient visual loss triggered by scuba diving in a patient with a petrous epidermoid and combined thrombotic risk factors.

    PubMed

    Fodor, Mariann; Facskó, Andrea; Berényi, Ervin; Sziklai, István; Berta, András; Pfliegler, György

    2007-01-01

    A 25-year-old woman who developed transient neurological abnormalities after scuba diving is reported. The subsequent day she experienced transient left-side monocular blindness. Arterial ocular occlusion in apparently healthy young women is unusual, and a search for the cause of this devastating vascular event is mandatory. Occlusion of the left branch retinal artery, total occlusion of the left internal carotid artery, and a petrous apex epidermoid were found, together with a shortened prothrombin time (INR: 0.73), a slightly elevated serum cholesterol level (6.1 mmol/l) and combined thrombophilia (elevated FVIIIC plus type 2 sticky platelet syndrome). This case underlines the complex mechanism of thromboembolic diseases, and the importance of the acquired trigger (in the present case scuba diving) in addition to the long-term anatomical and biochemical risk factors.

  18. Acquiring case adaptation knowledge: A hybrid approach

    SciTech Connect

    Leake, D.B.; Kinley, A.; Wilson, D.

    1996-12-31

    The ability of case-based reasoning (CBR) systems to apply cases to novel situations depends on their case adaptation knowledge. However, endowing CBR systems with adequate adaptation knowledge has proven to be a very difficult task. This paper describes a hybrid method for performing case adaptation, using a combination of rule-based and case-based reasoning. It shows how this approach provides a framework for acquiring flexible adaptation knowledge from experiences with autonomous adaptation and suggests its potential as a basis for acquisition of adaptation knowledge from interactive user guidance. It also presents initial experimental results examining the benefits of the approach and comparing the relative contributions of case learning and adaptation learning to reasoning performance.

  19. Acquire CoOmmodities Easily Card

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for helpmore » with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.« less

  20. Acquired alexia: lessons from successful treatment.

    PubMed

    Beeson, P M; Insalaco, D

    1998-11-01

    Two individuals with anomic aphasia and acquired alexia were each provided treatment for their reading impairment. Although reading of single words in isolation was fairly accurate, their text reading was slow and effortful, including functor substitutions and semantic errors. Prior to treatment, reading reaction times for single words showed grammatical class and word-length effects. Both patients responded positively to a treatment protocol that included two phases: (1) multiple oral rereading of text, and (2) reading phrase-formatted text that had increased spacing between phrasal clauses. Their reading rates for text improved while maintaining good comprehension. Following treatment, reading reaction times for single words showed the elimination of grammatical class and word-length effects, suggesting improved access to word forms, particularly functors.

  1. Acquire CoOmmodities Easily Card

    SciTech Connect

    Soler, E. E.

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for help with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.

  2. Stereotypic movement disorder after acquired brain injury.

    PubMed

    McGrath, Cynthia M; Kennedy, Richard E; Hoye, Wayne; Yablon, Stuart A

    2002-05-01

    Stereotypic movement disorder (SMD) consists of repetitive, non-functional motor behaviour that interferes with daily living or causes injury to the person. It is most often described in patients with mental retardation. However, recent evidence indicates that this condition is common among otherwise normal individuals. This case study describes a patient with new-onset SMD occurring after subdural haematoma and brain injury. SMD has rarely been reported after acquired brain injury, and none have documented successful treatment. The current psychiatric literature regarding neurochemistry, neuroanatomy, and treatment of SMD are reviewed with particular application to one patient. Treatment options include serotonin re-uptake inhibitors, opioid antagonists and dopamine antagonists. SMD has been under-appreciated in intellectually normal individuals, and may also be unrecognized after brain injury. Further investigation is needed in this area, which may benefit other individuals with SMD as well.

  3. The acquired immunodeficiency syndrome in gay men.

    PubMed

    Jaffe, H W; Hardy, A M; Morgan, W M; Darrow, W W

    1985-11-01

    The acquired immunodeficiency syndrome (AIDS) is a major health problem for gay men in the United States. About three fourths of all reported cases have occurred in this population, and the number is projected to double in the next year. In Manhattan and San Francisco, AIDS is now the leading cause of premature mortality in men aged 25 to 44 years who have never married. In a sample of a cohort of gay men enrolled in a San Francisco clinic, 2.7% of the men had the syndrome and 26% had related conditions in 1984. Antibody to human T-lymphotropic virus, type III/lymphadenopathy-associated virus was found in sera from 67% of the men, including 58% of asymptomatic men. Behavioral factors associated with an increased risk of AIDS include large numbers of sexual partners, receptive anal intercourse, and "fisting." The adoption of safer lifestyles is currently the basis of attempts to control the syndrome in gay men.

  4. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  5. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  6. Antihelper T cell autoantibody in acquired agammaglobulinemia.

    PubMed Central

    Rubinstein, A; Sicklick, M; Mehra, V; Rosen, F S; Levey, R H

    1981-01-01

    A patient with acquired agammaglobulinemia had an antihelper T cell factor that was identified as an immunoglobulin of the IgG class. The factor specifically bound to the TH2- T cell subset and, in the presence of complement, abolished the helper effect of normal T cells. The antihelper T cell antibody preceded by several years the appearance of suppressor TH2+Ia+ T cells, at which time the clinical course rapidly deteriorated. Plasmapheresis resulted in lymphocytosis and reappearance of a functionally intact helper T cell population. It did not affect the suppressor cells. Conversely, total thymectomy resulted in a temporary disappearance of the TH2+Ia+ suppressor cells, but did not decrease the levels of the autoantibody to helper T cells. Neither of these treatments reversed the state of agammaglobulinemia. PMID:6450224

  7. Acquired methaemoglobinaemia related to phenazopyridine ingestion.

    PubMed

    Shahani, Lokesh; Sattovia, Stacy

    2012-09-17

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population.

  8. Acquired methaemoglobinaemia related to phenazopyridine ingestion

    PubMed Central

    Shahani, Lokesh; Sattovia, Stacy

    2012-01-01

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population. PMID:22987905

  9. Multiple myeloma associated with acquired cutis laxa.

    PubMed

    Cho, S Y; Maguire, R F

    1980-08-01

    Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

  10. Guidelines for prevention of hospital acquired infections

    PubMed Central

    Mehta, Yatin; Gupta, Abhinav; Todi, Subhash; Myatra, SN; Samaddar, D. P.; Patil, Vijaya; Bhattacharya, Pradip Kumar; Ramasubban, Suresh

    2014-01-01

    These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. PMID:24701065

  11. Infantile and acquired nystagmus in childhood.

    PubMed

    Ehrt, Oliver

    2012-11-01

    Nystagmus is an involuntary, periodic eye movement caused by a slow drift of fixation which is followed by a fast refixation saccade (jerk nystagmus) or a slow movement back to fixation (pendular nystagmus). In childhood most cases are benign forms of nystagmus: idiopathic infantile, ocular or latent nystagmus. They arise at the age of 3 months, without oscillopsia and show the absence of the physiologic opto-kinetic nystagmus. A full ophthalmologic evaluation is all that is needed in most cases: albinism, macular or optic nerve hypoplasia and congenital retinal dystrophies are the most common forms of ocular nystagmus. Idiopathic infantile nystagmus can be hereditary, the most common and best analyzed form being a mutation of the FRMD7 gene on chromosome Xq26.2. The mutation shows a mild genotype-phenotype correlation. In all female carriers the opto-kinetic nystagmus is absent and half had mild nystagmus. Latent nystagmus is part of the infantile esotropia syndrome and shows the unique feature of change of direction when the fixing eye changes: it is always beating to the side of the fixing eye. There is no cure for infantile nystagmus but therapeutic options include magnifying visual aids or eye muscle surgery at the age of 6-8 y in patients with head turn. Less than 20% of childhood nystagmus are acquired and need further neurological and imaging work-up. Alarming signs and symptoms are: onset after the age of 4 months, oscillopsia, dissociated (asymmetric) nystagmus, preserved opto-kinetic nystagmus, afferent pupillary defect, papilloedema and neurological symptoms like vertigo and nausea. The most common cause is due to pathology of the anterior optic pathway (e.g. optic nerve gliomas). It shows the same clinical feature of dissociated nystagmus as spasmus nutans but has a higher frequency as in INO. Other forms of acquired nystagmus are due to brainstem, cerebellar or metabolic diseases. PMID:22459007

  12. 48 CFR 970.4102 - Acquiring utility services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Acquiring utility services... SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Acquisition of Utility Services 970.4102 Acquiring utility services....

  13. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of Land... of acquisition by the Bureau of Land Management, and are not subject to the requirements of § 4110.1....

  14. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  15. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  16. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  17. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  18. Preschoolers Acquire General Knowledge by Sharing in Pretense

    ERIC Educational Resources Information Center

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  19. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Disposition of acquired property. 1779.90 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  20. 7 CFR 770.8 - Use of acquired land.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Use of acquired land. 770.8 Section 770.8 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.8 Use of acquired land. (a) General. Subject to § 770.5(d) land acquired with loan funds, or other property serving as the security for a...

  1. 25 CFR 211.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2011-04-01 2011-04-01 false Government employees cannot acquire leases. 211.8...

  2. 25 CFR 212.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ALLOTTED LANDS FOR MINERAL DEVELOPMENT General § 212.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2011-04-01 2011-04-01 false Government employees cannot acquire leases. 212.8...

  3. 25 CFR 212.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ALLOTTED LANDS FOR MINERAL DEVELOPMENT General § 212.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2010-04-01 2010-04-01 false Government employees cannot acquire leases. 212.8...

  4. 25 CFR 211.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2010-04-01 2010-04-01 false Government employees cannot acquire leases. 211.8...

  5. Acquired prosopagnosia: structural basis and processing impairments.

    PubMed

    Davies-Thompson, Jodie; Pancaroglu, Raika; Barton, Jason

    2014-01-01

    Cognitive models propose a hierarchy of parallel processing stages in face perception, and functional neuroimaging shows a network of regions involved in face processing. Reflecting this, acquired prosopagnosia is not a single entity but a family of disorders with different anatomic lesions and different functional deficits. One classic distinction is between an apperceptive variant, in which there is impaired perception of facial structure, and an associative/amnestic variant, in which perception is relatively intact, with subsequent problems matching perception to facial memories, because of either disconnection or loss of those memories. These disorders also have to be distinguished from people-specific amnesia, a multimodal impairment, and prosop-anomia, in which familiarity with faces is preserved but access to names is disrupted. These different disorders can be conceived as specific deficits at different processing stages in cognitive models, and suggests that these functional stages may have distinct neuroanatomic substrates. It remains to be seen whether a similar anatomic and functional variability is present in developmental prosopagnosia.

  6. Acquiring synaesthesia: insights from training studies

    PubMed Central

    Rothen, Nicolas; Meier, Beat

    2014-01-01

    Synaesthesia denotes a condition of remarkable individual differences in experience characterized by specific additional experiences in response to normal sensory input. Synaesthesia seems to (i) run in families which suggests a genetic component, (ii) is associated with marked structural and functional neural differences, and (iii) is usually reported to exist from early childhood. Hence, synaesthesia is generally regarded as a congenital phenomenon. However, most synaesthetic experiences are triggered by cultural artifacts (e.g., letters, musical sounds). Evidence exists to suggest that synaesthetic experiences are triggered by the conceptual representation of their inducer stimuli. Cases were identified for which the specific synaesthetic associations are related to prior experiences and large scale studies show that grapheme-color associations in synaesthesia are not completely random. Hence, a learning component is inherently involved in the development of specific synaesthetic associations. Researchers have hypothesized that associative learning is the critical mechanism. Recently, it has become of scientific and public interest if synaesthetic experiences may be acquired by means of associative training procedures and whether the gains of these trainings are associated with similar cognitive benefits as genuine synaesthetic experiences. In order to shed light on these issues and inform synaesthesia researchers and the general interested public alike, we provide a comprehensive literature review on developmental aspects of synaesthesia and specific training procedures in non-synaesthetes. Under the light of a clear working definition of synaesthesia, we come to the conclusion that synaesthesia can potentially be learned by the appropriate training. PMID:24624072

  7. Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

    PubMed Central

    Collins, F M

    1989-01-01

    The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population. PMID:2680057

  8. [Acquired and congenital heart diseases during pregancy].

    PubMed

    De Feo, Stefania; Iacovoni, Attilio; Faggiano, Pompilio

    2012-05-01

    Heart diseases are the leading cause of maternal morbidity and mortality. The number of patients with congenital heart diseases reaching childbearing age, as well as the proportion of women with acquired conditions, such as ischemic heart disease, becoming pregnant is constantly increasing. All women with known heart disease should have pre-pregnancy counseling, to assess maternal and fetal risk. Women at moderate or high risk should be under the care of a specialist prenatal team with experience in managing women with heart disease during pregnancy. Conditions that are considered at particularly high risk (mortality >10%) include Marfan syndrome with dilated aortic root, severe left ventricular dysfunction, severe left heart obstructive lesions, and pulmonary hypertension. Peripartum cardiomyopathy is a rare and potentially fatal disease related to pregnancy and the postnatal period that presents with symptoms of congestion and/or hypoperfusion and may rapidly progress to acute and life-threatening heart failure. However, the majority of women with heart disease can tolerate pregnancy; therefore an adequate multidisciplinary approach with the gynecologist, anesthesiologist and cardiologist should be advocated in order to reduce maternal and fetal risks associated with pregnancy.

  9. Community-acquired pneumonia among smokers.

    PubMed

    Almirall, Jordi; Blanquer, José; Bello, Salvador

    2014-06-01

    Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities.

  10. Community-acquired pneumonia among smokers.

    PubMed

    Almirall, Jordi; Blanquer, José; Bello, Salvador

    2014-06-01

    Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities. PMID:24387877

  11. Community-acquired pneumonia: An overview.

    PubMed

    Mandell, Lionel A

    2015-08-01

    Community-acquired pneumonia is still a significant cause of morbidity and mortality and is often misdiagnosed and inappropriately treated. Although it can be caused by a wide variety of micro-organisms, the pneumococcus, atypicals, such as Mycoplasma pneumoniae and Chlamydophila pneumoniae, Staphylococcus aureus and certain Gram-negative rods are the usual pathogens encountered. The site-of-care decision is critical in determining the site and type of care as well as the extent of diagnostic workup. Antimicrobial therapy should be started as soon as possible particularly in those requiring admission to hospital, but typically the physician does not know with any degree of certainty the identity of the etiologic pathogen. A number of national guidelines have been published to help the physician with this choice. The initial drug(s) can be modified if necessary if the pathogen and its antimicrobial susceptibility pattern becomes known. Adjunctive therapy such as pressors and fluid replacement are of value and macrolides appear to help as well, likely secondary to their immunomodulatory effects. Recent data also suggest a role for steroids.

  12. [Severe community-acquired pneumonia in adults].

    PubMed

    Arancibia H, Francisco; Díaz P, Orlando

    2005-01-01

    Patients with severe community acquired pneumonia (CAP) need continuous surveillance and monitoring at intensive care units (ICU), where they can receive specialized support as mechanical ventilation and/or hemodynamic support. Patients that require ICU admittance represent 10 to 30% of all patients interned because a pneumonia. In this category, high complication rate, prolonged hospital stay and high mortality rate are the rule. The American Thoracic Society (ATS) criteria for severe pneumonia establishes the following main criteria: necessity of mechanical ventilation and presence of septic shock; minor criteria: systolic blood pressure < 90 mmHg, radiological multilobar involvement and PaO2/FiO2 < 250 mmHg. British Thoracic Society (BTS) criteria for severe CAP are: respiratory rate over 30 breaths/min, diastolic blood pressure under 60 mmHg, BUN > 20 mg/dl and mental confusion. In all patients with CAP it is recommended the evaluation of its severity at admission. This evaluation should be done in conjunction with an experienced physician, and if criteria for poor prognosis are met, an early admission to ICU is recommended. ATS and BTS modified criteria (CURB) are useful in this procedure. In severely ill patients with CAP it is recommended to perform the following microbiological analysis: sputum Gram stain and culture, blood culture, pleural fluid Gram stain and culture, if present and tapped, Legionella pneumophila urine antigen test, influenza A and B antigen detection tests (epidemic period: autumn and winter), and serology for atypical bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae).

  13. Acquired Hemophilia A Successfully Treated with Rituximab

    PubMed Central

    D’Arena, Giovanni; Grandone, Elvira; Di Minno, Matteo Nicola Dario; Musto, Pellegrino; Di Minno, Giovanni

    2015-01-01

    Acquired hemophilia A (AHA) is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm., but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs) remains to be established and warrants further investigation. PMID:25745551

  14. Acquired hemophilia a successfully treated with rituximab.

    PubMed

    D'Arena, Giovanni; Grandone, Elvira; Di Minno, Matteo Nicola Dario; Musto, Pellegrino; Di Minno, Giovanni

    2015-01-01

    Acquired hemophilia A (AHA) is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm., but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs) remains to be established and warrants further investigation. PMID:25745551

  15. Community-acquired Pneumonia and its Complications.

    PubMed

    Qin, Qiang; Shen, Kun-ling

    2015-08-01

    Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide in developing and developed countries, and its incidence is highest among children less than 5-y-old. Over the last five years, several international and local guidelines have been updated with new evidence concerning the epidemiology, etiology, pathogenesis, treatment and prevention of pediatric CAP, but there are still several major problems that need to be standardised. The aim of this review is to consider the available data concerning the termination, epidemiology, microbiology and pathogenesis, clinical features, diagnosis and differential diagnosis, treatment, and complications of pediatric CAP. There still are many unanswered questions concerning the management of CAP, including its definition, the difficulty to identify its etiological agents, the emergence of drug, and the lack of introduction of vaccines against respiratory pathogens in developing countries. More research is required in various areas (including therapy of atypical agents), and further efforts are needed to increase vaccination in order to reduce the incidence of the disease. PMID:25976616

  16. Salmonella acquires ferrous iron from haemophagocytic macrophages.

    PubMed

    Nagy, Toni A; Moreland, Sarah M; Detweiler, Corrella S

    2014-09-01

    Bacteria harbour both ferrous and ferric iron transporters. We now report that infection of macrophages and mice with a Salmonella enterica Typhimurium strain containing an inactivated feoB-encoded ferrous iron transporter results in increased bacterial replication, compared to infection with wild type. Inactivation of other cation transporters, SitABCD or MntH, did not increase bacterial replication. The feoB mutant strain does not have an intrinsically faster growth rate. Instead, increased replication correlated with increased expression in macrophages of the fepB-encoded bacterial ferric iron transporter and also required siderophores, which capture ferric iron. Co-infection of mice with wild type and a feoB mutant strain yielded a different outcome: FeoB is clearly required for tissue colonization. In co-infected primary mouse macrophages, FeoB is required for S. Typhimurium replication if the macrophages were IFNγ treated and contain phagocytosed erythrocytes, a model for haemophagocytosis. Haemophagocytes are macrophages that have engulfed erythrocytes and/or leucocytes and can harbour Salmonella in mice. These observations suggest that Salmonella acquires ferrous iron from haemophagocytic macrophages.

  17. [Acquired polycystic degeneration of the kidneys].

    PubMed

    Kreisel-Büstgens, C; Büstgens, L; Graben, N

    1990-12-15

    Kidneys of patients with advanced renal insufficiency undergo polycystic transformation, described as acquired cystic degeneration (ACD). In 118 chronic dialysis patients clinical data were compared with sonographic findings of their 221 cirrhotic kidneys: 74 (63%) patients showed distinctly discernible renal cysts: 19 patients hat one single cyst, nine patients had two to eight cysts, 46 patients had more than eight cysts. Accordingly 39% of patients had ACD. Cystic transformation was of the same degree on both sides and in a few cases so marked that a formal discrimination to congenital cystic disease seemed impossible. Cystic degeneration was not influenced by patient's age, sex or underlying renal disease, but was dependent on the duration of both, renal disease and dialysis treatment. After eight years 71% of dialysis patients had ACD. In coincidence with cystic transformation the size of the kidneys apparently normalized and Hb-concentration rose from 8 to 10 g/dl. Complications were seen in six patients: two severe retroperitoneal bleedings and four hypernephroma were observed. The etiology of cystic transformation and its possible role as precancerosis are discussed.

  18. Acquired prosopagnosia abolishes the face inversion effect.

    PubMed

    Busigny, Thomas; Rossion, Bruno

    2010-09-01

    Individual faces are notoriously difficult to recognize when they are presented upside-down. Since acquired prosopagnosia (AP) has been associated with an impairment of expert face processes, a reduced or abolished face inversion effect (FIE) is expected in AP. However, previous studies have incongruently reported apparent normal effects of inversion, a decreased or abolished FIE, but also a surprisingly better performance for inverted faces for some patients. While these discrepant observations may be due to the variability of high-level processes impaired, a careful look at the literature rather suggests that the pattern of FIE in prosopagnosia has been obscured by a selection of patients with associated low-level defects and general visual recognition impairments, as well as trade-offs between accuracy and correct RT measures. Here we conducted an extensive investigation of upright and inverted face processing in a well-characterized case of face-selective AP, PS (Rossion et al., 2003). In 4 individual face discrimination experiments, PS did not present any inversion effect at all, taking into account all dependent measures of performance. However, she showed a small inversion cost for individualizing members of a category of non-face objects (cars), just like normal observers. A fifth experiment with personally familiar faces to recognize confirmed the lack of inversion effect for PS. Following the present report and a survey of the literature, we conclude that the FIE is generally absent, or at least clearly reduced following AP. We also suggest that the paradoxical superior performance for inverted faces observed in rare cases may be due to additional upper visual field defects rather than to high-level competing visual processes. These observations are entirely compatible with the view that AP is associated with a disruption of a process that is also abolished following inversion: the holistic representation of individual exemplars of the face class.

  19. Impact of lactobacilli on orally acquired listeriosis

    PubMed Central

    Archambaud, Cristel; Nahori, Marie-Anne; Soubigou, Guillaume; Bécavin, Christophe; Laval, Laure; Lechat, Pierre; Smokvina, Tamara; Langella, Philippe; Lecuit, Marc; Cossart, Pascale

    2012-01-01

    Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect of treatment with each Lactobacillus on L. monocytogenes counts in host tissues and showed that each decreases L. monocytogenes systemic dissemination in orally inoculated mice. A whole genome intestinal transcriptomic analysis revealed that each Lactobacillus changes expression of a specific subset of genes during infection, with IFN-stimulated genes (ISGs) being the most affected by both lactobacilli. We also examined microRNA (miR) expression and showed that three miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes infection. Treatment with each Lactobacillus increased miR-192 expression, whereas only L. casei association increased miR-200b and miR-215 expression. Finally, we showed that treatment with each Lactobacillus significantly reshaped the L. monocytogenes transcriptome and up-regulated transcription of L. monocytogenes genes encoding enzymes allowing utilization of intestinal carbon and nitrogen sources in particular genes involved in propanediol and ethanolamine catabolism and cobalamin biosynthesis. Altogether, these data reveal that the modulation of L. monocytogenes infection by treatment with lactobacilli correlates with a decrease in host gene expression, in particular ISGs, miR regulation, and a dramatic reshaping of L. monocytogenes transcriptome. PMID:23012479

  20. [Clinical aspects of acquired antithrombin III deficiency].

    PubMed

    von Blohn, G; Hellstern, P; Köhler, M; Scheffler, P; Wenzel, E

    1986-02-01

    The significance of acquired antithrombin III (AT III) deficiency must be interpreted in close relation to the underlying disease process. In patients with acute or chronic liver impairment, the AT III activity is related to a decrease of procoagulatory factors, whereas, in protein loss syndromes such as nephrotic syndrome, the AT III indicates an increased risk of thromboembolic events. The effect of oral contraceptives (OC) on AT III levels in young healthy females (n = 30) was determined prospectively. AT III decreases during OC usage could not be related to the estrogen content of the examined oral contraceptives, and there was no parallel decrease of AT III activity and concentration in each type of OC. In a prospective study, the extent of AT III decrease was determined in patients undergoing cardiopulmonary bypass operations (CPB) receiving different anticoagulant schedules during extracorporeal circulation (n = 49). There was no significant influence on the effectiveness of anticoagulation by the observed AT III decreases. AT III deficiency during CPB was primarily the result of hemodilution. However, the AT III kinetics were significantly influenced by the different protamin dosages and were not affected by the different heparin dosages. Correction of diminished AT III levels by substitution of AT III concentrates is beneficial in cases, in which an interruption of an enhanced coagulatory process such as disseminated intravascular coagulation is necessary or in patients requiring high dosage heparinization as in deep vein thrombosis. In those cases the quality of AT III correction correlates to the course of the disease. However, the potency of concentrates as well as the individual AT III recovery and half-life must be considered for an appropriate treatment with AT III substitution. PMID:3718407