bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic Thrombocytopenic Purpura in a Patient with Sickle Cell Crisis.
Authors: Chatiwala Jumana S. , Guron Gunwant , Sidhom Ibrahim 
Published: April 2020

Abstract
Thrombotic thrombocytopenic purpura (TTP) in association with sickle cell crisis is rare. We present a case of sickle cell crisis and TTP. This is 48 years old Nigerian male with history of mild sickle cell anemia since childhood presented with sickle cell crisis and mental state changes. On admission labs are hematocrit of 20 and platelet count of 212,000. He was treated for sickle cell crisis but developed acute dysuria and progressively worsening anemia (Hct-13.7) and thrombocytopenia (Plt-9000) with sickle cell and fragmented RBCs on peripheral smear with LDH of 8772. This picture was consistent with TTP. Patient was immediately started on plasma exchange. Patient received a course of plasma exchange as well as hemodialysis and his condition improved, with return of platelet count to normal (232), LDH to baseline (276). Patient was discharged with mild renal insufficiency (serum creatinine-2.3) off dialysis and plasma exchange.
Conclusion: TTP is a micro vascular occlusive disorder characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. It is associated with pentard of signs and symptoms: thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral blood smear), neurological abnormalities, renal failure and fever. In practice thrombocytopenia, microangiopathic hemolytic anemia and elevated lactate dehydrogenase levels are often sufficient for the diagnosis. Our patient with sickle cell crisis was a diagnostic challenge and it is our belief that TTP evolved during inpatient therapy for painful crisis. We believe his hemolysis was due to sickle cell disease and TTP. The syndrome was reversed with prompt and aggressive treatment with plasmapharesis. (1, H. E. Lee, V. J. Marder, L. J. Logan, S. Friedman, B. J. Miller, Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease. Ann Hematol. 2003 Nov 82(11): 702–4. 2, Epub 2003 Aug 16. Chehal A, Taher A, Shamseddine A, Sicklemia with multi-organ failure syndrome and thrombotic thrombocytopenic purpura. Hemoglobin. 2002 Nov; 26(4): 345–51. 3, J. Bolanos-Meade, Y. K. Keung, C. Lopez-Arvizu, R. Florendo, E. Cobos, Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis. Ann Hematol. 1999 Dec 78(12): 558–9. 4, Geigel EJ, Francis CW, Reversal of multiorgan system dysfunction in sickle cell disease with plasma exchange. Acta Anaesthesiol Scand. 1997 May; 41(5): 647–50.)
Infectious Mononucleosis Presenting with Severe Thrombocytopenia, Positive Anti-Platelets Antibodies, and Peripheral Blood Blasts.
Authors: Haddad Rami Y. , Komrokji Rami S. 
Published: April 2020

Abstract
Case Report: 18 year old male presents with 2 weeks history of sore throat, fever, and hemoptysis. Physical examination revealed exudative and hemorrhagic tonsillo-pharyngitis, posterior cervical lymphadenopathy, mild splenomegaly, and petechieal rash involving the extremeties and the trunk. On presentation, CBC showed Hgb of 15.5gm/dl, WBCs of 11.8 K/uL, Platelets count of 4 K/uL. Differential count showed lymphocytes of 56%, reactive lymphocytes 1%. Monospot test was positive. CT abdomen confirmed the physical finding of splenomegaly, and showed mild hepatomegaly. Treatment was initiated with pulse methylprednisone 1g/d, and IVIG 1g/kg/day. Both were given for 2 days. One unit of SDP was transfused on days 2, 4, 5. On day 4 platelets count was 6 K/uL. 2–3% blasts were detected on the peripheral smear on days 4 and 5. Bone marrow biopsy and aspiration were done on day 5. They revealed reactive marrow changes with no increase in blasts. Flow cytometry revealed reactive marrow lymphocyte subpopulations and no inrease in immature myeloid cells. Subsequently, EBV serology was reported; EBV capsid IgM and IgG were both positive at &gt;4-fold higher than upper normal limit. In addition, Platelets antibodies were reported positive for IIB/IIIA, IB/IX, and IA/IIA. Platelets count on day 7 was 58 K/uL without platelets transfusion in the previous 24 hours.
Conclusion: Literature review reveals rare cases of Infectious Mononucleosis presenting with severe thrombocytopenia. Most of these cases were treated successfully with steroids and /or IVIG, similarly to ITP. However, no previous association with peripheral blood blasts has been described. Moreover, only two previous reports have described the association between Infectious Mononucleosis and the presence of platelets antibodies but without details of the receptors involved.
Dengue Fever and Thrombocytopenia: A Deadly Duo.
Authors: Lale Ajit , Lale Seema , Bick Rodger , Fareed Jawed 
Published: April 2020

Abstract
Dengue fever (DF) is one of the most ill understood diseases of Asian Pacific countries which is associated with reversible vascular complications. These complications are part of severe manifestations of Dengue Haemorregic Fever (DHF) and Dengue Shock Syndrome (DSS) which can be prevented with early detection and appropriate interventions. Increased hematocrit, elevated liver enzymes, altered coagulation profile and decreased platelet count are some of the parameters which predicts severity of this disease. Thrombocytopenia is always considered a predictive parameter for the inpatient management of dengue fever as well as recovery parameter in DHF and DSS. We examined 28 reviews and original articles out of 175 listed in “Pub med” on Dengue Fever and thrombocytopenia to find any possible relevance with the pathophysiology of thrombocytopenia and clinical bleeding in dengue across the spectrum of disease. Correlation between platelet counts and development of clinical bleeding was also studied as well as diagnostic markers for early detection. Finally, we summarize recent reports on treatment of thrombocytopenia, including evidence for conservative use of platelet transfusions and briefly complications of platelet transfusions. Thrombocytopenia is the most common laboratory finding in dengue patients, most patients manifesting petechiae, epistaxis, and mild mucosal bleeding. Severe hemorrhage is catastrophic and associated high mortality. Close monitoring of the patient for hemorrhagic manifestations and marked thrombocytopenia is strongly recommended. Other modalities include transfusion therapy with supportive therapy.
Inverse Correlation of Serum Leptin Levels and Platelet Counts in Patients with Menstruation-Associated Cyclic Thrombocytopenia.
Authors: Kameoka Junichi , Yamada Minami , Kadowaki Ikuko , Kaku Mitsuo , Sasaki Takeshi 
Published: April 2020

Abstract
The platelet counts of patients with cyclic thrombocytopenia (CT) are occasionally associated with menstruation, yet its mechanism is unknown. Leptin has been shown to stimulate the production of Th1 cytokines (Nature1998;27:897), which dominate in idiopathic thrombocytopenic purpura (ITP) (Blood2004;103:2645), and a recent study showed that the serum levels of leptin, whose secretion is menstruation-related, are high in ITP (Eur J Haemataol2004;72:348). Here we examined the serial serum levels of leptin in 3 patients with CT by radioimmunoassay. Case 1 is a 29-year-old woman with ITP who had repeated spontaneous abortion at an early phase of pregnancy accompanied by transient severe thrombocytopenia. Case 2 is a 37-year-old woman diagnosed as having ITP and autoimmune neutropenia during her second pregnancy, whose platelet counts became cyclic after delivery. Case 3 is a 28-year-old woman, who developed CT after splenectomy performed for refractory ITP two years before. The serum leptin levels were inversely correlated with the platelet counts in case 1 (r = −0.573, P =0.047, n=13) and case 3 ( r = −0.771, P =0.029, n=9), and a similar inverse correlation was observed in case 2, although the correlation was statistically not significant (r = −0.524, P=0.116, n=10). These findings suggest that leptin might play an important role in the pathogenesis of menstruation-associated CT. Further interventional studies to give leptin and its antagonists to the patients with CT, as well as to ITP model mice, will be warranted.
Association between Platelet Autoantibody Specificity and Response to Intravenous Immunoglobulin G in the Treatment of Patients with Immune Thrombocytopenia.
Authors: Johnston Kaye L. , Go Ronald S. 
Published: April 2020

Abstract
Background: Recent studies in murine model of immune thrombocytopenia (ITP) suggest that autoantibodies against GPIba may cause thrombocytopenia through Fc-independent pathway and ITP mediated by anti-GPIb may be less responsive to intravenous immunoglobulin G (IVIG) treatment (Nieswandt B, et al. Blood 2000; Webster ML, et al. Blood 2006). The objective of this study was to investigate the potential association between platelet autoantibody specificity and response to intravenous immunoglobulin G (IVIG) treatment in patients with ITP.
Methods: We retrospectively reviewed the clinical history of ITP patients who had platelet autoantibody test and received IVIG for treatment of thrombocytopenia. ITP was diagnosed by usual clinical criteria. All platelet autoantibody tests were performed by the Blood Center of Wisconsin (Milwaukee, WI) using ELISA, which detects antibodies reactive with platelet GPIIb/IIIa, GPIb/IX, and GPIa/IIa. A response was defined as a platelet count of &gt; 50 x 109/L with a minimum increment of 30 x 109/L.
Results: We found 17 patients who received IVIG and had platelet autoantibody test performed. The median age was 58 years (range, 20–83) and 10 (59%) were males. ITP was considered idiopathic in 12 patients. In the remaining 5 patients, the following hematologic conditions were present: chronic lymphocytic leukemia (2), Hodgkin lymphoma (1), myelodysplastic syndrome (1), and non-Hodgkin lymphoma (1). Antibodies reactive with GPIIb/IIIa, GPIb/IX, and GPIa/IIa were detected in 13, 10, and 8 patients, respectively. In 3 patients, none of these antibodies were detected. Among the 14 patients with antibodies, 9 (64%) had antibodies against more than 1 glycoprotein. The median pre-treatment platelet count was 9 x 109/L (range, 1–68). Overall, 10 (59%) patients responded to IVIG. A response occurred in 7 of 7 patients without anti-GPIb/IX but in only 3 of 10 patients with anti-GPIb/IX. The difference in the response rates between the 2 groups was statistically significant (P= .0098).
Conclusions: Our clinical results support the murine model findings that ITP mediated by anti-GPIb may be less responsive to IVIG treatment. However, because of the small number of patients investigated and the retrospective nature of the study, our findings must be confirmed by other groups in a larger patient population.
Thrombotic Thrombocytopenic Purpura: Is Plasma Exchange Enough? A Fifteen Year Australian Experience at the Royal Melbourne Hospital.
Authors: Ng Ashley P. , Frawley Natasha , Hogan Chris , Grigg Andrew , Cohney Solomon , Nicholls Kathy , Becker Gavin 
Published: April 2020

Abstract
Introduction Thrombotic Thrombocytopenic Purpura (TTP) is a cause of microangiopathic-haemolytic anaemia and thrombocytopenia, associated with renal and neurological dysfunction with thrombotic complications causing significant morbidity and mortality.
Methods A restrospective single-institution analysis of patients with TTP treated between 1990–2005. Renal or bone marrow transplantation patients were excluded.
Results Forty patients were identified. Aetiology was idiopathic 75% (n=30), connective tissue disease-related 12.5% (n=5), malignancy-related 5% (n=2) and pregnancy-related 7.5% (n=3). Presenting features: neurological 62.5% (n=25), renal impairment (creatinine&gt;0.11 mmol/L) 76% (n=28), microangiopathic-haemolytic anaemia 97.5% (n=39) and thrombocytopenia 100% (mean platelet-count 42x10^9/L). Mean Hb 93 g/L and mean Lactose dehydrogenase (LD) 2517 U/L (&lt;420). 38 patients received up-front single plasma-volume plasma-exchange using fresh-frozen plasma (median 11 exchanges). All received steroids. Complete-response (CR) (normalisation of platelet count, LD, neurological examination and rising Hb), was achieved in 79% (n=30) following plasma-exchange of whom 43% (n=13) relapsed (median 14.5 days from therapy-cessation): eleven achieved CR2 with further therapy and two died from TTP-related complications. Partial-response (PR) was obtained in 7.9% (n=3) with up-front plasma-exchange: one remained in PR with prostate-cancer treatment and two relapsed: one achieved CR and one sustained-PR with further therapy. 13% (n=5) were refractory to plasma-exchange: four died from TTP-related complications and one achieved CR with treatment intensification. Therapeutic intensification included steroids (n=34), vincristine (n=7), intravenous immunoglobulin (n=6), Rituximab (n=3) and splenectomy (n=6).
Conclusion TTP is associated with a significant relapse-rate (43%) and TTP-related mortality (16%) despite plasma-exchange. Delineation of patients at high risk of relapse following CR will potentially allow targetted treatment intensification. Treatment intensification is also clearly required for patients with refractory TTP and consideration may be given to other immunosuppressive agents, such the chimeric monoclonal anti-CD20 antibody, Rituximab, as a steroid-sparing agent and to potentially avoid splenectomy. We propose a central TTP registry is developed within Australia such that therapeutic strategies can be systematically evaluated in a multicentre setting.
Autologous Human Thrombin: Production from Whole Blood.
Authors: Kumar Vijay , Chapman John R. 
Published: April 2020

Abstract
Introduction: Thrombin is routinely combined in surgical practice with a fibrinogen source to prepare fibrin sealant to promote hemostasis or with platelet concentrates to prepare platelet gels to enhance wound healing and reduce infections. Currently, thrombin is derived either from bovine tissue or “pooled” human plasma. The purpose of this study was to evaluate the robustness and reproducibility of a new sterile handheld disposable TPD™ (Thrombin Processing Device) to generate autologous human thrombin in the intra-operative setting, using whole blood as the starting source material. By using whole blood instead of plasma as the starting material, it is possible to eliminate the plasma separation step from whole blood and reduce the thrombin production time and increase its availability to the surgical team intra-operatively. The performance of the disposable set was evaluated at the low and high end of operating room temperatures.
Materials and Methods: Active thrombin was prepared by combining 4 ml of thrombin reagent (a mixture of calcium chloride and ethanol) to 11 ml of blood in a reaction chamber containing negatively charged particles. The whole blood, reagent and particle mixture was incubated for 25 minutes at either 18°C or 24°C (n=25/group) to assess stability of the thrombin activity.
Results: The average activity of the thrombin produced at 18°C and 24°C was 52 ± 14 IU/ml (n=25) and 61 ± 12.2 IU/ml (n=25), respectively. The average volume of thrombin harvested from each aliquot of blood was 9 ± 0.6 ml in both groups. The thrombin concentration generated was demonstrated to rapidly (&lt;5 seconds) coagulate fibrinogen concentrate and retained clotting activity for 1 hr at room temperature (18 - 26 oC) and up to 4 hours when stored on ice.
Conclusions: The results demonstrate that the TPD is able to consistently generate high thrombin activity from human whole blood. The device offers a robust and rapid approach for preparing active thrombin from whole blood. By eliminating the risk for allergic reactions and blood borne pathogen transmission, autologous human thrombin can be considered as a safer alternative to bovine or “pooled” plasma sourced thrombin.
Association between the Plasminogen Activator Inhibitor-1 4G/5G Gene Polymorphism and Ischemic Stroke; a Meta-Analysis.
Authors: Nikolopoulos Georgios K. , Tsantes Argirios E. , Bagos Pantelis G. , Tsiara Chrissa G. , Mantzios Georgios P. , Kapsimali Violetta , Pappa Vassiliki , Travlou Anthi S. 
Published: April 2020

Abstract
The relationship between the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 (PAI-1) gene and ischemic stroke (IS), remains unclear. This association has received less attention compared with the relation with coronary heart disease. Since stroke is the third commonest cause of death in the developed world, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until January 2006 and the analysis was performed using random effects models and meta-regression.
A total of 15 eligible case-control studies were considered. The analysis included 3104 cases and 4870 controls regarding the contrast of 4G/4G vs. the rest genotypes. The 4G pooled allele frequency in cases and controls was 54.21% and 54.75% respectively. Overall, the per-allele Odds Ratio (OR) of the 4G allele was 0.98 with a 95% Confidence Interval (CI) 0.858 to 1.121. As concerns genotypes, we derived non-significant ORs in all contrasts. Our findings do not support a significant association between the 4G/5G polymorphism and cerebrovascular disease under basal conditions. However, the influence of this genotype on the risk of IS in acute disorders might require further investigation, since PAI-1 seems to act as an acute-phase reactant.
The Genetics of Hemostasis: Heritability of Clotting Factor Concentrations in 224 Pediatric Stroke Families.
Authors: Nowak-Gottl Ulrike , Bergs Sandra , Thedieck Sabine , Stoll Monika 
Published: April 2020

Abstract
Background and objectives: Earlier studies found a strong support for a genetic basis for regulation of coagulation factor levels. The present study was conducted to estimate the variation within coagulation factors levels, and how much of this variation could be attributed to heritability and household effect in pediatric stroke families.
Methods: Blood samples were collected from 853 individuals from 224 white pediatric stroke pedigrees (male 51.3%). Heritability (h2r) and household effect (c2) were estimated for plasma concentrations of fibrinogen, factor (F) II, V, VIIIC, vWF, antithrombin, protein C, protein S, protein Z, prothrombin fragment F1.2 and D-dimer using the variance component method in sequential oligo-genetic linkage analysis routines (SOLAR).
Results: When incorporating h2r and c2 in one model, high and significant h2r estimates were found for protein Z (31.7), protein S (27.5), fibrinogen 29.9) and von Willebrand factor (20.4). In addition to the significant h2r estimates c2 showed a significant effect on phenotypic variation for protein Z (26.0), protein S (22.2) and vWF (14.8). A significant household effect without h2r interaction was found for FVIIIC (30.7), FII (25.6), protein C and FV (12.0).
Conclusion: In the cohort investigated we have shown that genetic factors have a major effect on plasma concentrations of coagulation factors. Our research stresses the importance of research into the genetic regulation of proteins involved in hemostasis associated with pediatric stroke.
Prevalence of Cross Reactive Epitopes to Bovine Factor Va Light Chain Fragments in Normal and Patients Plasma.
Authors: Hoppensteadt Debra A. , Bansal Vinod , Cunanan Josephine , Patel Kuldeep , Wahi Rakesh , Fareed Jawed 
Published: April 2020

Abstract
Several reports have described the presence of antibodies to bovine coagulation factors, such as factor V, prothrombin and factor X in plasma samples obtained from patients exposed to topical bovine thrombin. Other reports have also demonstrated the presence of anti-bovine coagulation factors in patients who have not been exposed to bovine thrombins, suggesting that anti-bovine protein antibodies can be generated in normal individuals. It has been suggested that surgical patients treated with topical bovine thrombin develop specific antibodies to bovine factor V which may be responsible for the bleeding and thrombotic complications. However, there is no definitive clinical study demonstrating a relationship between the apparent hemostatic defects and the presence of bovine factor Va antibodies. It was hypothesized that bovine factor Va antibodies are usually present in patients plasma because of the exposure to dietary bovine products. To test this hypothesis plasma samples from patients with end state renal disease (ESRD)(n=80), acute coronary syndrome (ACS)(n=160), burns (n=40) and healthy normal volunteers (n=140) were profiled for the presence of human factor V antigen (HFVA), bovine FVa antigen as measured by using a modified Elisa method and western blotting methods where bovine factor Va light chain fragment is used as a probe. In contrast to the normals (89±12%), the factor V antigen levels were found to be increased in the ESRD (148±30%), ACS (164±41%) and burn (145±27%) patients. Thus, there appears to be an up regulation of factor V antigen in these patients. All of the groups tested for the presence of immunoreactive material to the bovine factor Va light chain exhibited 2–3 ug/ml levels which were not significantly different. However, in the western blotting studies all groups exhibited cross reactivity with the factor Va light epitopes. There were bands present in the molecular weight range of 22, 36, 45 and 97 Kda in both the ESRD and burn patients. In the ACS patients there was an additional band observed at 166 Kda. These observations underscore the notion that bovine antifactor Va antibodies are non-specific and highly prevalent in both the surgical/interventional patients and normal population. A possible explanation for the presence of these antibodies is that most normal individual and patients problem are exposed to bovine proteins. Moreover, the higher prevalence of these antibodies in the ESRD and ACS patients may be due to additional exposure to heparin and aprotonin.