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Biomedical subjects

Gail Rock

Publications and source records attributed to Gail Rock.

10 recordsLinked to original sources
PubMed2006

Identification of plasma antifibrin/fibrinogen antibodies in a patient with hemolytic uremic syndrome.

We investigated a patient with atypical hemolytic uremic syndrome without diarrhea to determine the presence of antibodies and the specificity of the related antigens. The patient experienced repeated episodes of hemolytic uremic syndrome. She is dialysis dependent. von Willebrand factor (vWF), vWF multimers, platelet aggregation, ADAMTS-13 activity and platelet immunoblots were determined. During acute episodes vWF increased threefold, with unusually large vWF multimers on two occasions. Platelet aggregation was normal but the plasma caused spontaneous aggregation of normal platelets. Reactivity was removed after absorption with protein A. Protein blotting against platelet and microvascular endothelial cells showed strong and persistent reactivity against antigens of 200 and 55 kDa. Two-dimensional immunoblots of the whole platelet proteome and incubation with plasma identified strong immunoreactivity with two target spots in the 55-kDa area. Mass spectroscopy confirmed the target as beta-fibrin, molecular weight 50.73 kDa, isoelectric point 7.95, with MASCOT scores of 859 and 750, Two years after presentation another band was detected at 66 kDa and identified as the alpha subunit of fibrin. This patient's plasma contained a platelet-aggregating factor that was removed by immunoglobulin absorption. She developed antibodies against the alpha and beta subunits of fibrin/fibrinogen.

ADAM Proteins↗
PubMed2005

The management of thrombotic thrombocytopenic purpura in 2005.

Thrombotic thrombocytopenic purpura is an uncommon disease that often presents with a striking and acute clinical picture. Although first described more than 80 years ago, the therapy has changed little since the discovery that plasma, and then plasma exchange, could bring about a remarkable response, changing survival rates from 20% to more than 80%. However, although plasma exchange is now considered the standard of care, there is still considerable discussion concerning the appropriate schedules for therapy and the types of fluids that should be used. Because plasma exchange (PE) is not effective in all patients, and at least 30% of patients will have one or more relapses, several adjuvant therapies have also been used. Most recently, this has included the use of rituximab to achieve an immunomodulatory effect.

Antibodies, Monoclonal↗
PubMed2005

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

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.

ADAM Proteins↗
PubMed2005

Haemolytic uraemic syndrome is an immune-mediated disease: role of anti-CD36 antibodies.

Haemolytic uraemic syndrome (HUS) is a disorder in which platelet microthrombi are formed that have a particular propensity to deposit in the kidney microvasculature, resulting in impaired renal function and thrombocytopenia. The mechanism of formation of these microthrombi is not known. In this study, we showed that plasma from five adult and six paediatric cases of HUS caused aggregation and release of adenosine triphosphate from normal platelets. The plasma reacted against platelet lysate in a protein blot and all samples showed reactivity against a band at 88 kDa, corresponding to the membrane antigen CD36. This was confirmed by probing with Mo91, a monoclonal antibody to CD36. CD36 was also identified in the immune complex formed by incubation of patient plasmas with normal platelet lysate. In other studies, bands of 32 and 7.7 kDa were obtained when purified verotoxin was protein blotted and probed with either patient plasma or with anti-CD36 antibody Mo91 suggesting structural homologies between CD36 and verotoxin. While a direct cause-effect relationship is not yet established, the data support the concept of an immunological pathogenesis for HUS and suggest that molecular mimicry involving one or both of the homologous domains in membrane-bound CD36 and verotoxin lead to the development of antibodies capable of inducing the pathophysiological events characteristic of HUS.

ADAM Proteins↗
PubMed2003

Is there a need for a national or a global apheresis registry?

Indications for apheresis may vary and more than 45 different diagnoses have been reported from various countries. New devices are being developed and, in the beginning their clinical implications and use are limited to detect rare but important side effects. However, to achieve more reliable information on the effects and side effects we need more extensive sampling of data. Collection of such data is considered a safety and quality issue in several countries. However, data is still limited and little is known about therapeutic apheresis practised around the world including the incidence and pattern of adverse events. The establishment of national registries and analyses of data on a global level therefore seems important. Thus the World Apheresis Association (WAA) has initiated a global apheresis registry for therapeutic procedures and collection of e.g., stem cells. The WAA registry is Internet based and the site is at www.iml.umu.se/medicin. A login code to test the registry is needed (AL61TMS). This report deals with the aim of a global registry as well as some comparative data regarding findings of the Canadian, French and Swedish registries.

Blood Component Removal↗
PubMed2003

Seven-day storage of random donor PLT concentrates.

BACKGROUND: PLT concentrates are licensed for use up to a maximum of 5 days of storage. Increasing storage to 7 days would improve the logistics of supply and have the potential to reduce wastage. STUDY DESIGN AND METHODS: PLTs were prepared from CP2D blood with standard procedures (n = 16) and then WBC-reduced. Sampling was carried out at 3, 5, and 7 days for PLT count, pH, aggregation to ADP and collagen, hypotonic shock response, Kunicki morphology score, thromboelastogram response, pO2, and pCO2, and PLT activation (CD62) was carried out by flow cytometry. Additionally, PLTs stored for 7 days were transfused into thrombocytopenic patients, and the CCI was calculated. RESULTS: Some of the in vitro tests such as the aggregation response to single stimuli showed decreased values with time. The hypotonic shock was well maintained for 7 days (77%-68%); the Kunicki morphology score showed progressive shape change (300 to 164). The CCI of 7-day PLTs averaged 16,000 (n = 9). CONCLUSIONS: The data indicate acceptable in vitro PLT function at 7 days. Transfusion of the 7-day-old CP2D PLTs resulted in an appropriate posttransfusion increment in thrombocytopenic patients. Random donor PLTs collected into CP2D can be successfully stored for 7 days before use.

Blood Donors↗
PubMedDate not supplied

Normal functional protein S activity does not exclude protein S deficiency.

Protein S (PS) deficiency appears to increase the risk of venous thrombosis. PS deficiency is classified into three phenotypes using antigenic levels and functional activity. By definition, all three phenotypes of PS deficiency should result in low activated protein C cofactor activity. We compared the results of functional PS activity testing to free antigenic PS testing in order to determine if a normal functional PS activity assay result could eliminate the need for free antigenic PS testing. The sensitivity of the functional assay is 45.5% (95% confidence interval, CI, 36-55%), specificity 95.3% (95% CI 93-97%), negative predictive value 88.6% (95% CI 86-91%) with a positive predictive value of 68.5% (95% CI 57-79%). In conclusion, a normal functional PS activity result does not exclude free antigenic PS deficiency. Functional PS activity testing should not be used as a screening test to eliminate free antigenic PS testing for the laboratory diagnosis of PS deficiency.

Activated Protein C Resistance↗