bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sucessful Outcome in Poor-Prognosis Acute Thrombotic Thrombocitopenic Purpura Treated with Plasma Exchange and Rituximab.
Authors: Neto Cesar Almeida , Mendonça Mirianceli C. , Braga Marcelo C. , Ghaname Fabiana S. , Gobette Fernanda , Silva Luis F.F. , Ghaname Jorge N. , Gamne Anis 
Published: October 2019

Abstract
Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease that must be diagnosed and treated promptly for a successful outcome.
Case Report: In February 2005, a 44-year-old woman was admitted with severe microangiopathic hemolytic anaemia, jaundice, fever, seizures followed by coma and hypovolemic shock. She had joint pain 20 days before admission (anti-nuclear factor positive; 1/160) and had short-term episodes of bizarre behavior 1 week before admission. Her LDH was 2,860 IU/L; platelet count 37,000/mm3; hemoglobin 5.1 g/dl; blood smears contained schistocytes; AST 240 U/L; ALT 166 U/L; HIV and hepatitis seronegative, and CT normal at admission. TTP was diagnosed and pulse methylprednisolene initiated (1 g iv for 3 days) with single-volume daily plasma exchange using fresh frozen plasma. After two sessions, there was marginal neurological improvement, platelet count increased to 95,000/mm3 and LDH decreased to 2,199 IU/L. After six plasma exchanges, neurological status worsened, LDH increased sharply (7,139 IU/L) as did ALT (1,700 U/L), AST (3,000 U/L) and platelet count was 72,000/mm3. Rituximab (four, weekly 375 mg/m2 doses) and plasma exchange with cryosupernatant substitution fluid were initiated. The first plasma exchange was postponed until 24 hours after the first dose of rituximab and 48 hours after subsequent doses. Within two days, there was neurological improvement, stable platelet levels and decreased LDH. Complete remission was achieved after 23 plasma exchanges and four doses of Rituximab. Plasma exchange was tapered and the patient remained in sustained remission until now. There were episodes of hives related to plasma exchange, but no toxicity related to rituximab.
Conclusion: Plasma exchange with cryosupernatant substitution fluid and rituximab had an important role in the successful treatment of this patient - a systematic clinical trial setting should be considered in order to confirm these findings.
Familial Thrombotic Thrombocytopenic Purpura in Three Siblings.
Authors: Niewiadomska Edyta , Budde Ulrich , Anna Klukowska 
Published: October 2019

Abstract
Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia, systemic platelet aggregation, organ ischemia, thrombocytopenia, and fragmentation of erythrocytes. The disease is caused either by congenital deficiency of von Willebrand factor-cleaving protease (ADAMTS 13) or due to acquired autoantibodies against ADAMTS 13. We have been treating three siblings with recurrent episodes of hemolytic anemia, thrombocytopenia, neurological and renal dysfunctions during last 10 years. The oldest brother presented with thromboangiopathic anemia, thrombocytopenia (platelets account below 30x103/μl), episode of unconsciousness, proteinuria and splenomegaly at the age of 15 years. Splenectomy was done with the improvement in thrombocytopenic purpura. But he has suffered from permanent microangiopathic hemolytic anemia, and developed renal insufficiency. He died due to intestinal bleeding last year. Two younger siblings, a 12 year old girl and an 11 year old boy also presented with recurrent symptoms of microangipathic hemolytic anemia and thrombopcytopenia with or without renal dysfunction since early childhood. The diagnosis of congenital TTP in this family was based on clinical symptoms and tests of ADAMTS 13 and its inhibitor. The activity of ADAMTS 13 in two younger siblings performed according to the method of Gerritsen et al. was unmeasurable (<3%, reference range 30 – 120%). The ADAMTS 13 inhibitor was undetectable. Both patients are treated with fresh frozen plasma (FFP) infusions every 4 weeks. Precise diagnosis is very important for proper treatment. Only regular FFP infusions as ADAMTS 13 supplementation can assure normal health condition of children with familial TTP.
Critical Role of the Blood Coagulation in Malaria: Plasmodium falciparum-Infected Red Blood Cells Induce Tissue Factor Expression by Endothelial Cells and Support the Assembly of Coagulation Complexes.
Authors: Francischetti Ivo M.B. , Seydel Karl B. , Monteiro Robson Q. 
Published: October 2019

Abstract
Malaria is still the world’s most important parasitic disease and is responsible for the death of more people than any other communicable disease except tuberculosis. According to WHO estimates, 300–500 million people are infected with malaria every year. Deaths occur mostly among young children in Africa. Cerebral malaria (CM) is the most severe complication and accounts for up to 80% of fatal cases of Plasmodium falciparum malaria. The mechanisms of malaria and CM pathogenesis remain the subject of continuing debate. It is believed that hemostatic alterations could be of importance in the disease since P. falciparum malaria has been associated with thrombocytopenia and hemostatic alterations (pro-coagulant state), by an unknown mechanism. Here we demonstrate that P. falciparum-infected red blood cells (IRBC) induce Tissue Factor (TF) expression by endothelial cells in culture, in a parasitemia- and time-dependent manner. Tissue Factor was consistently detected by functional (Factor Xa formation), antigen (ELISA), and RT-PCR. Remarkably, only mid-late but not early trophozoites and ring stage parasites were capable of inducing TF expression. These findings are compatible with post-mortem brain biopsies where sequestration is composed mostly by late-stage trophozoites. Our experiments also demonstrate that late-stage IRBC support the assembly of the prothrombinase complex in the presence of FVa, FXa, prothrombin and Ca2+ with thrombin formation. IRBC also support the intrinsic Xnase assembly in the presence of FIXa, FVIIIa, FX and Ca2+ with generation of FXa. It is concluded that IRBC manipulates the hemostatic system by initiating the blood coagulation cascade through induction of TF expression by endothelial cells, leading to FXa production. FXa and other components of the prothrombinase complex assemble in the IRBC allowing the coagulation cascade to propagate, with thrombin formation. Thrombin, FXa and FVIIa may also activate the pro-inflammatory PAR receptors in endothelial cells creating a unique inflammatory environment in the vessels where sequestration has occurred. These finding introduces the concept that malaria is an inflammatory syndrome triggered by expression of TF and activation of the coagulation cascade. Identification of TF as a critical mediator of malaria may allow investigators to test other therapeutic alternatives targeting TF in the treatment of malaria.
Viral Safety of a Novel Von Willebrand Factor and Factor VIII Concentrate (Wilate®): Virus Inactivation Capacities of Optimised Solvent/Detergent and Terminal Dry-Heat Treatment (PermaHeat).
Authors: Biesert Lothar , Suhartono Haryadi , Klengel Rolf , Schmidt Torben , Radomski Kai-Uwe , Schwarz Gerhard , Gruber Gerhard , Stadler Monika , Neisser-Svae Andrea , Roemisch Juergen , Svae Tor-Einar 
Published: October 2019

Abstract
Purpose: The virus inactivation capacities of the optimised solvent/detergent (S/D) and terminal dry-heat (PermaHeat) treatments, as part of the Wilate® manufacturing process, were determined in this study. Wilate® is a novel, human plasma-derived, VWF/FVIII concentrate, which through the clinical trials has been proven safe and effective in the treatment of von Willebrand disease and haemophilia A patients.
Methods: S/D virus inactivation studies were performed in down-scaled settings using 1% Octoxynol/0.3% TNBP for 4 hours at +23–28°C. PermaHeat was performed at +100°C for 120 min at 0.6% residual moisture in the lyophilisate (0.7–1.6% during regular manufacturing). Robustness conditions were studied for both steps.
Summary of results: S/D treatment revealed the following inactivation ratios [log10]: HIV-1: ≥7.5, SBV: ≥8.6 and PRV: ≥8.5. All enveloped viruses (EV) were inactivated below the detection limits of the infectivity assays already after 2 minutes. Variation of process parameters did not reduce the efficacy of the S/D treatment. For PermaHeat the following inactivation ratios were found at extreme conditions, i.e. low residual moisture [log10]: EV: HIV-1: ≥5.8, SBV: ≥5.5 and PRV: 4.9 - NEV (non-enveloped viruses): REO-3: ≥6.4, HAV: ≥5.7, PPV: 4.1.
Conclusion: The Wilate® manufacturing process comprises two dedicated, efficient and robust virus inactivation steps, S/D and PermaHeat treatments. The total capacities [log10] for the individual viruses amount to ≥13.3 for HIV-1, ≥14.1 for SBV, ≥13.4 for PRV, ≥6.4 for REO-3, ≥5.7 for HAV, and 4.1 for PPV. Other production steps may contribute to virus reduction as well.
Significance and Study of Fibrinolytic System in Pleural and Ascitic Fluid.
Authors: Lu Xingguo , Mao Mao Jianshan , Liu Jin , Zhang Xiaohong , Zhao Xiaoying , Xu Genbo , Gong Xubo , Yang Zhongguo 
Published: October 2019

Abstract
Objective: To study significance and character of fibrinolytic system in pleural and ascitic fluid with three disease.
Methods: Urokinase plasminogen activator (uPA), urokinase plaminogen activator receptor (uPAR) were measured by ELISA, tissue plaminogen activator (tPA), plaminogen activator inhibitor-1(PAI-1), plasminogen (Plg), plasmin (Pl), and a2 plasmin inhibitor (a2PI) by colorimetric assay.
Result: The levels of uPA and uPAR in pleural and ascitic fluid were marked higher in malignant tumor (2533.42±1369.89 ng/L and 7.32±1.59μg/L) and tuberculosis (2618.05±1542.50 ng/L, 8.75±3.48μg/L)than in cirrrhosis (961.25 ± 692.82ng/L and 2.73±1.59 μg/L, P<0.01). The level of tPA was marked higher in cirrhosis (353.75±142.31 IU/L) and malignant tumor (341.16±136.46 IU/L) than in tuberculosis(266.45±43.70 IU/L, P<0.01). The levels of PAI-1, Plg and Pl were in order of quantity tuberculosis(828.02±217.02 AU/L, 5.17±1.51 IU/ml and 65.52±25.22%), malignant tumor (540.35±217.52 AU/L, 3.90±1.25 IU/ml and 49.52±14.27%), cirrhosis (337.88±162.03 AU/L, 1.88±0.51 IU/ml and 26.04±8.45%). There were significant difference among them (P<0.01). The level of a2PI was marked higher in malignant tumor (82.38±28.68%) and cirrhosis (91.75±24.73%) than in tuberculosis (61.62±27.67%, P<0.05). Among seven targets in malignant tumor group, only the level of uPA was significant difference between positive group in pleural and ascitic fluid with cancer cell (3073.44±1161.93μg/L) and negative group without cancer cell (1453.38±1128.39μg/L, P<0.01).
Conclusions: There were significant difference in fibrinolytic charater in pleural and ascitic fluid with different diseases. To join test with fibrinolysis targets can not only help determine quality of pleural and ascitic fluid, but also can help deeply understand pathologic processes in desease, especially some biologic actions of malignant tumor.
Clinical Diagnosis and Management of Children with Large Splenic Hemangiomas Accompanied with Consumptional Coagulopathy.
Authors: Ci Pan , Jing Chen , Lu Dong , Jingyan Tang , Yaoping Wang 
Published: October 2019

Abstract
Objective To improve the diagnosis and treatment of children with large splenic hemangiomas accompanied with consumptional coagulopathy.
Methods From Dec 2003 to May 2004, 2 children with large splenic hemangiomas and coagulational abnormality were admitted consecutively. Both of them were boys, aged 2.8 and 3.5 years old, respectively. Both of them had splenomegaly, and Patient 2 also had multiple bone hemangiommas(confirmed by biopsy before splenectomy) on addmission. Imaging studies failed to confirm the diagnosis of splenic hemangiomas. Both of them received 24 hours continuous subcutaneous injection of Nadroparin Calcium therapy and the coagulopathies were improved. Then, Patient 1 had splenectomy, and Patient 2 received Nadroparin Calcium therapy plus steroid and interferon therapy for 6 months, then also went to splenectomy.
Results Both of the two patients had normal platelet counts and normal coagulation parameters just after their splenectomies. Histology studies confirmed the diagnoses of splenic cavernous hemangiomas. Before splenectomy, Patient 2 had a stable status for 6 months after he received Nadroparin Calcium therapy plus interferon and steroid therapy. Till March 31th, 2005, Patient 1 had disease free for 13 months, and Patient 2 had normal platlet counts and normal coagulation parameters for 5 month besides his stable multiple bone lessions.
Conclusion Childhood large splenic hemangioma accompanied with consumptional coagulopathy is a rare disease, which can be cured by splenectomy. Before operation, it is necessary to improve the coagulation abnormality, and 24 hours continuous subcutaneous Nadroparin Calcium injection plus coagulation factors transfusion is effective.
Hemostasis with Erythropoietin in Massive, Uncontrollable, Diffuse GI Bleeding.
Authors: Zaharia Veronica C. , Zaharia Daniel R. 
Published: October 2019

Abstract
Purpose: Erythropoietin currently used as a hemopoietic agent, has remarkable hemostatic activity which can be lifesaving in diffuse, uncontrollable bleeding processes. Following is an example case report:
Case presentation: 47 y/o male was admitted with massive GI bleeding and a Hemoglobin (Hg) of 6.7 mg/dl requiring transfusion of 26U Packed Red Blood Cells {PRBC) and 9U of Fresh Frozen Plasma (FFP). The work up revealed a large cell lymphoma infiltrating the mesenteric lymph nodes, the retroperitoneum and the spleen. The small intestine was diffusely infiltrated and bleeding. A portion of the small intestine was resected in an attempt to stop the bleeding; still, the bleeding continued and the Hg could not be raised above 7.8. Erythropoietin 20,000U was administered subcutaneously on day 9 to help correct the anemia. An additional 40,000U were administered on day 14 and 21. Three days after the 2nd dose of Erythropoietin the bowel movement did not appear grossly bloody, the Hg stabilized, and chemotherapy could be administered. After discharge with a follow up of 10 months his Hg stabilized at 12–12.5 mg/dl without any bleeding or transfusion.
Discussion: Erythropoietin has been shown to shorten the bleeding time in chronic renal failure patients on hemodialysis by improving the platelet/subendotelial cell interaction and by raising the platelet count. An enhanced platelet aggregation in response to Ristocetin was noted in Erythropoietin treated uremic patients. This effect was correlated with a rise in platelet Serotonin. Erythropoietin also has been found to have a procoagulant effect in uremic patients by decreasing the protein C, protein S, antithrombin III level. These observations offer an explanation for the clinically observed hemostatic effect of Erythropoietin.
Conclusion: This and other cases have shown that Erythropoietin is a potent hemostatic factor in anemic patients with diffuse uncontrollable bleeding processes, where large amounts of transfused PRBC can barely keep up with the losses and hemostatic procedures can either not be done or failed. As more experience accumulates Erythropoietin may start a second life as a hemostatic factor.
Figure Figure
The Behavior of Anticardiolipin Antibodies Levels in Patients with Venous Thromboembolism.
Authors: Martinez Aline A. , Rodrigues Celso A. , Morelli Vania M. , Noguti Maria Aparecida E. , Andrade Luis Eduardo C. , Lourenco Dayse M. 
Published: October 2019

Abstract
The aim of this study was to investigate anticardiolipin (aCL) (IgG and IgM) levels in patients with objectively confirmed venous thromboembolism (VTE). aCL IgG and IgM were measured using an in-house ELISA assay. When aCL levels were ≥10 U, a second measurement was performed using another sample at least 6 weeks after the first test. Patients tested twice with aCL levels ≥10 U were classified as having positive aCL and those with only one measurement ≥10 U had transitory aCL. aCL was evaluated in 282 outpatients with VTE, with median age of 39 years (range:15–94), 66.7% were women. We found 28 patients (9.9%) with positive aCL (IgG in 5.6%, IgM in 1.8% and IgG + IgM in 2.5%) and 29 (10.3%) with transitory aCL (IgG in 5.3%, IgM in 3.2% and IgG + IgM in 1.8%). The association of systemic disease with VTE had a significant effect on the occurrence of transitory aCL (OR= 3.6; 95%CI: 1.5–8.8), but not on positive aCL (OR= 1.7; 95%CI: 0.6–5.0). There was a significant correlation between the first and second measurements for IgG (rs= 0.58; p < 0.0001) and for IgM (rs= 0.49; p = 0.011). Patients with IgG < 30 GPLU showed a higher risk of having transitory aCL (OR= 4.9; 95%CI: 1.2–19.7; p= 0.027), and this effect was more pronounced in patients with IgM < 30 MPLU (OR=15; 95%CI: 1.2 – 113.6; p= 0.008). In conclusion, prevalence of transitory aCL was as high as positive aCL in patients with VTE, mainly among those with IgG or IgM < 30 U. Higher aCL levels were more frequently associated with repeatedly positive aCL. Transitory aCL was more frequent in the presence of systemic disease associated with VTE, which could reflect an epiphenomenon, whereas repeatedly positive aCL could play a more important role in the genesis of VTE.
Antiphospholipid Antibody Syndrome: Annexin V Competitive Flow Cytometric Assay for Determination of Anti-Platelet Phospholipid Autoantibodies.
Authors: Tomer Aaron , Barlev Shira , Abu-Shakra Mahmoud , Shenkman Boris 
Published: October 2019

Abstract
A flow cytometric assay was developed for the determination of autoantibodies directed against platelet anionic-phospholipids in antiphospholipid syndrome (APS). The method is based on demonstrable competition between the placental anticoagulant protein I, annexin V, and the patients’ autoantibodies on the platelet anionic-phospholipids (the binding site for the prothrombinase complex; prothrombin, factors Va and Xa). The method is practical and rapid, uses readily available reagents, and standard equipment. Ninety-two plasma samples, 41 from patients with clinical diagnosis of APS, 27 from patients with systemic lupus erythematosus (SLE) and 24 from healthy individuals were analyzed. Thirty-five (85%) of patients with APS (either with or without SLE), 15 (94%) of patients with APS and SLE, and 20 (80%) of APS patients without SLE were positive. Nineteen (70%) out of 27 patients with SLE alone were also positive; of whom 15 (58%) were positive for either anti-cardiolipin antibody (ACL) or lupus anti-coagulant (LAC). Comparison with ACL showed 40 (93%) out of 43 patients positive for ACL were also positive by flow cytometry (FCM). However, 13 (48%) out of 27 patients negative for ACL were found positive by FCM. Seven of these patients have primary APS and 6 have SLE; 7 of whom were positive for LAC. Three (13%) out of the 24 control samples, all negative by FCM, were positive for ACL. Comparison with LAC showed 32 (91%) out of 35 patients positive for LAC also positive by FCM. Of 18 patients negative for LAC, 7 (39%) were negative and 11 (61%) were positive by FCM. Four of the 11 patients have a diagnosis of APS and 7 of SLE; 6 of whom were positive for ACL. None of the controls, all negative by FCM, was positive for LAC. In conclusion, the annexin V competitive flow cytometric assay for the determination of anti-platelet phospholipid autoantibodies maybe useful for the laboratory diagnosis of APS.
Cerebral Sinovenous Thrombosis Post Head Injury - 10 Year Experience in Children.
Authors: Komwilaisak Patcharee , Brandao Leonardo , Blaser Susan , Dirks Peter , deVeber Gabrielle , Williams Suzan , Chan Anthony K.C. , Ahbaya Kulkarni 
Published: October 2019

Abstract
Cerebral sinovenous thrombosis (CSVT) post head injury is infrequently diagnosed in children. We retrospectively reviewed 323 patients with histories of head injury and a computerized tomography scan of the head from June 1996 to June 2005. Twelve patients (3.7%) were diagnosed with CSVT. The mean age was 6 years (range from 2 to 15 years). Male to female ratio was 10:2. The mechanism of injury included motor vehicle accidents in 5 patients, and falls in 7 patients. Nine patients had minor head injuries (GCS> 8) whereas 3 patients had severe head injuries (GCS<8). The most common presenting symptom was vomiting in 5 patients and other less common symptoms including: headache, seizure and irritability. The commonest locations of thrombosis were sigmoid and transverse sinus. Four patients had extensive thrombus involving more than 3 sinuses. Of the 12 patients, 9 (75%) patients had skull fractures and 6 (50%) had epidural hematomas in association with CSVT. Seven patients (58%) received anticoagulant treatment. The duration of anticoagulant therapy was from 2 days to 6 months. Anticoagulation was discontinued in 3 patients (25%) due to extension of CNS bleeding. All patients receiving anticoagulation were therapeutic with an anti-factor Xa level of 0.5–1 units/mL on enoxaparin, 0.35–0.7 units/mL on standard heparin and INR level of 2–3 on Coumadin. There was complete resolution in 6 patients with the imaging done in a mean followup of 78.5 days, partial resolution in 3 patients with the mean followup imaging in 95.6 days, unchanged status in 1 patient 6 days after the diagnosis and no followup imaging in 2 patients. Six patients had thrombophilic work-up and all were normal. Of the 7 patients with full recovery, 3 patients did not receive anticoagulation. Four patients had seizure and headache, left hemiparesis, panhypopituitarism and optic atrophy, and attention deficit disorder, respectively. In conclusion, the prevalence of CSVT post head injury in children was approximately 3.7%. The etiology of CSVT in this situation might be associated with skull fracture and hematoma, which could compress the cerebral sinus. Large prospective studies involving multiple centers are required to ascertain whether prothrombotic investigations are necessary and if anticoagulation improves neurologic outcome in patients with CVST post head injury.