Research output per year
Research output per year
Abstract
The complement system is an essential effector of both innate and acquired immune responses. Due to its destructive potential, tight regulation is required. The contribution of complement has been associated with the pathogeneses in a wide range of diseases. In this thesis, aspects of complement activation were investigated in disorders characterized by thrombocytopenia.
In papers I and II, clinical characteristics, complement analyses, and genetic screening for rare variants encoding complement proteins were retrospectively investigated in a cohort suspected to suffer from atypical hemolytic uremic syndrome. In paper I, a population (n = 134) was identified whose phenotypes indicated the possibility of a diagnosis of complement-mediated atypical hemolytic uremic syndrome. In conclusion, laboratory complement analyses and clinical data were consistent with a possible underdiagnosis at the time of discharge. In paper II, recruited patients (n = 20) were subjected to follow-up investigations. Clinical outcomes and the phenotypical relevance of identified genetic variants were assessed. A diagnostic scheme compliant with the American College of Medical Genetics and Genomics guidelines was presented. In addition to identifying several previously described genetic variants, a novel likely disease-contributing missense variant in the complement factor H gene (c.3450A>G, p.I1150M) was identified. In conclusion, the study illustrated the risk of misdiagnosis and the importance of a comprehensive assessment to reach a diagnosis.
In paper III, complement and platelet activation biomarkers were prospectively investigated in thrombocytopenic patients (n = 43) receiving prophylactic platelet transfusions during inpatient care in the hematological department. Neither complement nor platelet activation was shown to correlate with the corrected count increment. In conclusion, complement and platelet activation were not demonstrated contributing to a poor post-transfusion platelet response.
In summary, this thesis has contributed to the growing knowledge of diseases potentially affected by complement activation.
In papers I and II, clinical characteristics, complement analyses, and genetic screening for rare variants encoding complement proteins were retrospectively investigated in a cohort suspected to suffer from atypical hemolytic uremic syndrome. In paper I, a population (n = 134) was identified whose phenotypes indicated the possibility of a diagnosis of complement-mediated atypical hemolytic uremic syndrome. In conclusion, laboratory complement analyses and clinical data were consistent with a possible underdiagnosis at the time of discharge. In paper II, recruited patients (n = 20) were subjected to follow-up investigations. Clinical outcomes and the phenotypical relevance of identified genetic variants were assessed. A diagnostic scheme compliant with the American College of Medical Genetics and Genomics guidelines was presented. In addition to identifying several previously described genetic variants, a novel likely disease-contributing missense variant in the complement factor H gene (c.3450A>G, p.I1150M) was identified. In conclusion, the study illustrated the risk of misdiagnosis and the importance of a comprehensive assessment to reach a diagnosis.
In paper III, complement and platelet activation biomarkers were prospectively investigated in thrombocytopenic patients (n = 43) receiving prophylactic platelet transfusions during inpatient care in the hematological department. Neither complement nor platelet activation was shown to correlate with the corrected count increment. In conclusion, complement and platelet activation were not demonstrated contributing to a poor post-transfusion platelet response.
In summary, this thesis has contributed to the growing knowledge of diseases potentially affected by complement activation.
| Original language | English |
|---|---|
| Qualification | Doctor |
| Awarding Institution |
|
| Supervisors/Advisors |
|
| Award date | 2022 Feb 8 |
| Place of Publication | Lund |
| Publisher | |
| ISBN (Print) | 978-91-8021-174-1 |
| Publication status | Published - 2022 |
Bibliographical note
Defense detailsDate: 2022-02-08
Time: 09:00
Place: Koagulationsmottagningens konferensrum, plan 3a, Jan Waldenströms gata 14, Skånes universitetssjukhus i Malmö. Join by Zoom: https://lu-se.zoom.us/j/69423976140?pwd=bXhzaW5Md1UzbEUzRzBVN3dwL21hUT09 Password: 004872
External reviewer(s)
Name: Wikman, Agneta
Title: Docent
Affiliation: Karolinska Institutet
Subject classification (UKÄ)
- Hematology
Free keywords
- Thrombocytopenia
- Complement activation
- Complement dysregulation
- Thrombotic microangiopathy
- Atypical hemolytic uremic syndrome
- Platelet transfusion refractoriness
Fingerprint
Dive into the research topics of 'Aspects of Complement Activation in Thrombocytopenic Disorders'. Together they form a unique fingerprint.Research output
- 3 Article
-
Biomarkers of complement and platelet activation are not correlated with the one or twenty-four hours corrected count increments in prophylactically platelet transfused hematological patients: a prospective cohort study
Åkesson, A., Ljungkvist, M., Martin, M., Blom, A. M., Klintman, J., Schött, U., Zetterberg, E. & Kander, T., 2022, In: Platelets. 33, 3, p. 350-359Research output: Contribution to journal › Article › peer-review
Open Access -
Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome: a Swedish retrospective observational study
Åkesson, A., Martin, M., Blom, A. M., Rossing, M., Gabrielaite, M., Zetterberg, E. & Klintman, J., 2021, In: Therapeutic Apheresis and Dialysis. 25, 6, p. 988-1000Research output: Contribution to journal › Article › peer-review
Open Access -
Indications of underdiagnosis of atypical haemolytic uraemic syndrome in a cohort referred to the Coagulation Unit in Malmo, Sweden, for analysis of ADAMTS13 2007–2012
Åkesson, A., Blom, A., Klintman, J. & Zetterberg, E., 2017 Jul 1, In: Nephrology. 22, 7, p. 555-561 7 p.Research output: Contribution to journal › Article › peer-review