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  • 1.
    Schmidt, David E.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Truedsson, Asa
    Karolinska Univ Hosp, Sweden.
    Stralfors, Annelie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Hojbjerg, Johanne Andersen
    Aarhus Univ Hosp, Denmark; Aarhus Univ, Denmark.
    Soutari, Nida
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Univ Hosp, Sweden.
    Ranta, Susanna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Letelier, Anna
    Lund Univ, Sweden.
    Bowyer, Annette
    Sheffield Teaching Hosp NHS Fdn Trust, England.
    Ljung, Rolf
    Lund Univ, Sweden.
    Antovic, Jovan
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bruzelius, Maria
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Clinical Implications of Discrepancy between One-Stage Clotting and Chromogenic Factor IX Activity in Hemophilia B2024Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, E-ISSN 2567-689X, Vol. 124, nr 01, s. 032-039Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with hemophilia B (PwHB) introduces challenges for clinical management.Aim To study the differences in FIX:C using OSA and CSA in moderate and mild hemophilia B (HB), their impact on classification of severity, and correlation with genotype.Methods Single-center study including 21 genotyped and clinically characterized PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories.Results FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe hemophilia type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A twofold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with diluted normal plasma, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories.Conclusion FIX:C was consistently higher by OSA compared with the CSA. Assessing FIX:C by CSA alone would have led to diagnosis of a more severe hemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify HB severity and provide essential information for clinical management.

  • 2.
    Lundin, Bjorn
    et al.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Baghaei, Fariba
    Sahlgrens Univ Hosp, Sweden.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Univ Hosp, Sweden.
    Petrini, Pia
    Karolinska Univ Hosp, Sweden.
    Mueller, Gunilla
    Stadtspital Triemli, Switzerland.
    Mansson, Sven
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Ljung, Rolf
    Lund Univ, Sweden.
    Haemophilia A and B - evaluation of the Swedish prophylactic regimen by magnetic resonance imaging2023Ingår i: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 29, nr 1, s. 193-198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IntroductionSweden has been a pioneer in the prophylactic treatment of haemophilia. Magnetic resonance imaging (MRI) can detect small changes in joints and can therefore give an indication of a risk of developing arthropathy. AimTo use MRI to evaluate the outcome of the Swedish high-dose regimen and correlate the findings to age, bleeds, joint score and physical activity. MethodsThe study group comprised 48 Swedish male patients, mean age 25 years (range 12-33 years), with severe or moderate haemophilia A or B. Data on the Haemophilia Joint Health Score (HJHS) were available and physical activity was evaluated by a self-reported questionnaire. ResultsMRI score was recorded in 188 joints. Twenty out of 48 patients had a score of >= 1 (range 1-13) in 31 joints of which 3/31 scores were in the knees and 28/31 in the ankles. No correlation was found between the number of recorded bleeds and the MRI score or between HJHS and MRI score. There was no correlation between the physical activity and the number of joint bleeds per se, but a trend (OR 3.0) that those most physically active (19/48; 39.6%), more frequently had an MRI score of >= 1 with an overweight for the right ankle. ConclusionThe Swedish prophylactic model offers protection against haemophilia joint arthropathy but will still not prevent osteochondral changes in some patients at young age. MRI of the ankles can signal risk of future arthropathy and indicate need to modify the prophylactic regimen.

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  • 3.
    Carlsson, Katarina Steen
    et al.
    Swedish Inst Hlth Econ, Sweden; Lund Univ, Sweden.
    Winding, Bent
    Swedish Orphan Biovitrum AB, Sweden.
    Astermark, Jan
    Skane Univ Hosp, Sweden.
    Baghaei, Fariba
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Brodin, Elisabeth
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Funding, Eva
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Univ Hosp, Sweden.
    Osterholm, Klaus
    Helsinki Univ Hosp, Finland.
    Bergenstrale, Sofia
    Swedish Orphan Biovitrum AB, Sweden.
    Lethagen, Stefan
    Swedish Orphan Biovitrum AB, Sweden.
    High use of pain, depression, and anxiety drugs in hemophilia: more than 3000 people with hemophilia in an 11-year Nordic registry study2023Ingår i: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, ISSN 2475-0379, Vol. 7, nr 2, artikel-id e100061Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pain is a common feature of hemophilia, but prevalence of depression and anxiety is less studied. Registry data on prescription drugs can provide an objective measure of the magnitude of these complications.Objectives: To identify treatment patterns of prescribed pain, antidepressant, and antianxiety medications compared with those of matched controls in 4 Nordic countries.Methods: The MIND study (NCT03276130) analyzed longitudinal individual-level national data during 2007-2017. People with hemophilia (PwH) were identified from National Health Data Registers by diagnosis or factor replacement treatment and compared with population controls. Three subgroups were defined by the use of factor concentrates and sex (moderate-to-high factor consumption (factor VIII [FVIII] use of =40 IU/kg/week or FIX use of =10 IU/kg/week), low factor consumption, and women including carriers).Results: Data of 3246 PwH, representing 30,184 person-years, were analyzed. PwH (including children and adults) used more pain, depression, and anxiety medications compared with controls. This was most accentuated in the moderate-to-high factor consumption group and notably also observed in men with low factor consumption and women including carriers, usually representing a milder phenotype. A higher opioid use was observed across all age groups: 4-to 6-fold higher in the moderate-to-high factor consumption group and 2-to 4-fold higher in the low factor consumption group.Conclusion: The consistent higher use of pain, depression, and anxiety medications among PwH compared with population controls, regardless of age, sex, or factor consumption, in broad national data suggests a need for improved bleed protection and hemophilia care for all severities including mild hemophilia.

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  • 4.
    Olsson, Anna
    et al.
    Sahlgrens Univ Hosp, Sweden.
    Westesson, Linda Myrin
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Baghaei, Fariba
    Sahlgrens Univ Hosp, Sweden.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Univ Hosp, Sweden.
    Olsson, Elsa
    Karolinska Univ Hosp, Sweden.
    Magnusson, Maria
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Ranta, Susanna
    Karolinska Univ Hosp, Sweden.
    Astermark, Jan
    Lund Univ, Sweden; Lund Univ, Sweden.
    Andersson, Nadine G. G.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Thanner, Judith
    Swedish Orphan Biovitrum AB, Sweden.
    Szamosi, Johan
    Swedish Orphan Biovitrum AB, Sweden.
    Daoura, Loudin
    Swedish Orphan Biovitrum AB, Sweden.
    Sennfaelt, Karin
    Swedish Orphan Biovitrum AB, Sweden.
    Real-world prophylactic usage of recombinant factor IX Fc in Sweden: A report from the Swedish National Registry for bleeding disorders2023Ingår i: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 29, nr 1, s. 377-381Artikel i tidskrift (Övrigt vetenskapligt)
  • 5.
    Boknäs, Niklas
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Laine, Cia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Hillarp, Andreas
    Oslo Univ Hosp, Norway.
    Macwan, Ankit
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten.
    Gustafsson, Kerstin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Associations between hemostatic markers and mortality in COVID-19-Compounding effects of D-dimer, antithrombin and PAP complex2022Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 213, s. 97-104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linkoping ¨ University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19− ). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers: high D-dimer, low antithrombin or low plasmin-antiplasmin complex (PAP) formation, with Odds Ratios (OR) for death of 4.7 (95% confidence interval (CI95) 1.7–12.9; p = 0.003) for D-dimer >0.5 mg/L, 5.9 (CI95 1.8–19.7; p = 0.004) for antithrombin (AT) ˂0.85 kIU/l and 4.9 (CI95 1.3–18.3; p = 0.019) for PAP < 1000 μg/L. Compounding increases in mortality was observed in COVID-19+ patients with combined defects in markers of fibrinolysis and coagulation, with ORs for death of 15.7 (CI95 4.3–57; p < 0.001) for patients with PAP <1000 μg/L and D-dimer >0.5 mg/L and 15.5 (CI95 2.8–87, p = 0.002) for patients with PAP <1000 μg/L and AT ˂0.85 kIU/L. We observed an elevated fraction of incompletely degraded D-dimer fragments in COVID-19+ patients with low PAP, indicating impaired fibrinolytic breakdown of cross-linked fibrin. 

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  • 6.
    Chowdary, Pratima
    et al.
    Royal Free Hosp, England.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Inst Solna, Sweden.
    Mahlangu, Johnny N.
    Univ Witwatersrand, South Africa; Natl Hlth Lab Serv, South Africa.
    Ozelo, Margaret C.
    Univ Estadual Campinas, Brazil.
    Pabinger, Ingrid
    Med Univ Vienna, Austria.
    Pasi, K. John
    Barts & London Queen Marys Sch Med & Dent, England.
    Ragni, Margaret V
    Univ Pittsburgh, PA USA; Univ Pittsburgh, PA USA.
    Shapiro, Amy
    Indiana Hemophilia & Thrombosis Ctr, IN USA.
    Barnowski, Chris
    Sanofi, MA USA.
    Lethagen, Stefan
    Swedish Orphan Biovitrum AB, Sweden; Univ Copenhagen, Denmark.
    Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: Data on safety and effectiveness from phase 3 pivotal studies2022Ingår i: Research and Practice in Thrombosis and Haemostasis, ISSN 2475-0379, Vol. 6, nr 5, artikel-id e12760Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Surgical procedures impose hemostatic risk to people with hemophilia, which may be minimized by optimal factor (F) replacement therapy. Methods This analysis evaluates the efficacy and safety of extended half-life factor replacement recombinant FVIII and FIX Fc fusion proteins (rFVIIIFc and rFIXFc) during surgery in phase 3 pivotal (A-LONG/Kids A-LONG and B-LONG/Kids B-LONG) and extension (ASPIRE and B-YOND) studies. Dosing regimens were determined by investigators. Injection frequency, dosing, blood loss, transfusions, and hemostatic response were assessed. Results Forty-five major (n = 31 subjects) and 90 minor (n = 70 subjects) procedures were performed in hemophilia A; 35 major (n = 22) and 62 minor (n = 37) procedures were performed in hemophilia B. Unilateral knee arthroplasty was the most common major orthopedic procedure (hemophilia A: n = 15/34; hemophilia B: n = 8/24). On the day of surgery, median total dose in adults/adolescents was 81 IU/kg for rFVIIIFc and 144 IU/kg for rFIXFc; most major procedures required &lt;= 2 injections (including loading dose). Through days 1-14, most major procedures had &lt;= 1 injection/day. Hemostasis was rated excellent (rFVIIIFc: n = 39/42; rFIXFc: n = 29/33) or good (n = 3/42; n = 4/33) in evaluable major surgeries, with blood loss comparable with subjects without hemophilia. Most minor procedures in adults/adolescents required one injection on the day of surgery, including median loading dose of 51 IU/kg (rFVIIIFc) and 80 IU/kg (rFIXFc). No major treatment-related safety concerns were identified. No subjects developed inhibitors or serious vascular thromboembolic events. Conclusions rFVIIIFc and rFIXFc were efficacious and well tolerated for the management of perioperative hemostasis across a wide spectrum of major and minor surgeries in hemophilia.

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  • 7.
    Carlsson, Katarina Steen
    et al.
    Swedish Inst Hlth Econ, Sweden; Lund Univ, Sweden.
    Winding, Bent
    Swedish Orphan Biovitrum AB, Sweden.
    Astermark, Jan
    Skåne Univ Hosp, Sweden.
    Baghaei, Fariba
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Brodin, Elisabeth
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Funding, Eva
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Univ Hosp, Sweden.
    Österholm, Klaus
    Helsinki Univ Hosp, Finland.
    Bergenstråle, Sofia
    Swedish Orphan Biovitrum AB, Sweden.
    Andersson, Emelie
    Swedish Inst Hlth Econ, Sweden.
    Lethagen, Stefan
    Swedish Orphan Biovitrum AB, Sweden.
    Pain, depression and anxiety in people with haemophilia from three Nordic countries: Cross-sectional survey data from the MIND study2022Ingår i: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 28, nr 4, s. 557-567Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction People with haemophilia (PwH) may experience symptoms of haemophilia-related pain, depression or anxiety, which can negatively impact health-related quality of life. Aim To obtain the perspective of PwH and treaters from Sweden, Finland and Denmark on the management of haemophilia-related pain, depression and anxiety using cross-sectional survey data from the MIND study (NCT03276130). Methods PwH or their caregivers completed a survey about experiences of pain, depression and anxiety related to haemophilia, and the standard EQ-5D-5L instrument. Five investigators at haemophilia treatment centres (HTC) were sent a complementary survey containing questions about the management of pain and depression/anxiety. Results There were 343 PwH (mild: 103; moderate: 53; severe: 180; seven lacking severity information) and 71 caregiver responses. Experience of pain in the last 6 months was reported by 50% of PwH respondents and 46% of caregiver respondents. Anxiety/depression was reported by 28% of PwH respondents. Reporting of pain and anxiety/depression was associated with disease severity. Whilst 62% of PwH who had experienced pain at any time point (n = 242) felt this was adequately addressed and treated at their HTC, only 24% of those who had experienced depression/anxiety (n = 127) felt this was adequately addressed. Disease severity was negatively associated with EQ-5D-5L utility value (p &lt; .001). In the HTC survey, 4/5 and 2/5 agreed that pain and depression/anxiety, respectively, are adequately addressed. Conclusions Pain and depression/anxiety occur more frequently with increasing haemophilia severity, with negative impacts on health-related quality of life. PwH with depression/anxiety or unaddressed pain could benefit from improved management strategies.

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  • 8.
    Szanto, Timea
    et al.
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Zetterberg, Eva
    Lund Univ, Sweden; Lund Univ, Sweden.
    Ramström, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Orebro Univ, Sweden.
    Leinoe, Eva B.
    Copenhagen Univ Hosp, Denmark.
    Holme, Pal A.
    Univ Oslo, Norway; Univ Oslo, Norway.
    Antovic, Jovan P.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Onundarson, Pall T.
    Univ Iceland, Iceland.
    Pikta, Marika
    North Estonia Med Ctr, Estonia.
    Vaide, Ines
    Univ Tartu, Estonia.
    Olsson, Anna
    Sahlgrens Univ Hosp, Sweden.
    Magnusson, Maria
    Sahlgrens Univ Hosp, Sweden.
    Kärkkäinen, Satu
    Fimlab Lab, Finland.
    Bitar, Manar
    Orebro Univ Hosp, Sweden.
    Poulsen, Lone Hvitfeldt
    Aarhus Univ Hosp, Denmark.
    Lassila, Riitta
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Platelet function testing: Current practice among clinical centres in Northern Europe2022Ingår i: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 28, nr 4, s. 642-648Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Platelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing. Aims To identify current practice among centres performing platelet function tests in Northern Europe. Methods A total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million. Results Six of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work-up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work-up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres. Conclusions The considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

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  • 9.
    Holmström, Margareta
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken. Karolinska Inst, Sweden.
    Olsson, Elsa
    Karolinska Inst, Sweden.
    Astermark, Jan
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Axelsson, Malin
    Skane Univ Hosp, Sweden.
    Olsson, Anna
    Sahlgrens Univ Hosp, Sweden.
    Myrin Westesson, Linda
    Sahlgrens Univ Hosp, Sweden.
    Falk, Aletta
    Swedish Orphan Biovitrum AB, Sweden.
    Szamosi, Johan
    Swedish Orphan Biovitrum AB, Sweden.
    Sennfalt, Karin
    Swedish Orphan Biovitrum AB, Sweden.
    Real-world prophylactic usage of recombinant factor VIII Fc in Sweden: A report from the Swedish national registry for bleeding disorders2021Ingår i: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 27, nr 4, s. e554-e558Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 10.
    Farm, Maria
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Antovic, Aleksandra
    Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Academic Specialist Center, Center for Rheumatology, Stockholm Health Services, Stockholm, Sweden.
    Schmidt, David E
    Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Coagulation Unit, Division of Haematology, Karolinska University Hospital, Stockholm, Sweden.
    Bark, Niklas
    Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Soutari, Nida
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Siddiqui, Anwar J
    Emergency Medicine Function, Karolinska University Hospital, Stockholm, Sweden.
    Holmström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Pruner, Iva
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Antovic, Jovan P
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Diagnostic Accuracy in Acute Venous Thromboembolism: Comparing D-Dimer, Thrombin Generation, Overall Hemostatic Potential, and Fibrin Monomers2020Ingår i: TH open : companion journal to thrombosis and haemostasis, ISSN 2512-9465, Vol. 4, nr 3, s. e178-e188Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction For acute venous thromboembolism (VTE), a biomarker with higher specificity than D-dimer would be of great clinical use. Thrombin generation and overall hemostatic potential (OHP) reflect the hemostatic balance by globally assessing multiple coagulation factors and inhibitors. These tests discriminate between healthy controls and patients with a prothrombotic tendency but have yet to be established as clinical biomarkers of VTE. Objective This study compares endogenous thrombin potential (ETP) and OHP to D-dimer and fibrin monomers (FM) in outpatients with suspected VTE. Methods A cross-sectional diagnostic study where 954 patients with suspected pulmonary embolism or deep venous thrombosis were recruited consecutively from the medical emergency department at Karolinska University Hospital. D-dimer, FM, OHP, and ETP were analyzed in a subpopulation of 60 patients with VTE and 98 matched controls without VTE. VTE was verified either by ultrasonography or computed tomography and clinical data were collected from medical records. Results Compared with healthy controls, both VTE and non-VTE patients displayed prothrombotic profiles in OHP and ETP. D-dimer, FM, ETP area under the curve (AUC), and ETP T lag were significantly different between patients with VTE and non-VTE. The largest receiver-operating characteristic AUCs for discrimination between VTE and non-VTE, were found in D-dimer with 0.94, FM 0.77, and ETP AUC 0.65. No useful cutoff could be identified for the ETP or the OHP assay. Conclusion Compared with D-dimer, neither ETP nor OHP were clinically viable biomarkers of acute venous thrombosis. The data indicated that a large portion of the emergency patients with suspected VTE were in a prothrombotic state.

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  • 11.
    Govorov, Igor
    et al.
    Karolinska Inst, Sweden.
    Bremme, Katarina
    Karolinska Inst, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Holmström, Margareta
    Karolinska Univ, Sweden.
    Komlichenko, Eduard
    Almazov Natl Med Res Ctr, Russia.
    Chaireti, Roza
    Karolinska Inst, Sweden.
    Mints, Miriam
    Karolinska Inst, Sweden.
    Thrombin generation during a regular menstrual cycle in women with von Willebrand disease2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 17467Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fluctuations of the sex steroids during the menstrual cycle might significantly influence hemostasis. This association, derived from a number of the observations on healthy women, is yet to be described in females affected by bleeding disorders. The aim of the current study was to assess the changes in hemostatic variables in women with vWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with healthy controls. The study group included 12 vWD-affected females with regular menstrual cycle, with none of them being prescribed any hormonal treatment. The control group consisted of 102 healthy females, matched for age and BMI. Within the vWD group FVIII and FX were both significantly higher during follicular phase than in luteal phase (p=0.013 and p=0.033 respectively). AT, FII, FVII and FX were higher in women with vWD, compared with controls during both phases of the menstrual cycle (pamp;lt;0.0005, pamp;lt;0.0005, p=0.001 and pamp;lt;0.0005). In women with vWD, lag time and time to peak were prolonged during both phases of the menstrual cycle(pamp;lt;0.0005), while peak thrombin concentration was reduced (p=0.003 and p=0.002 during follicular and luteal phase respectively) compared to healthy peers. Lower levels of FVIII and FX during luteal phase may predispose women to the development of the menorrhagia - common complication of vWD. Women with vWD need more time to reach the peak thrombin concentration, while the latter still remains less than in healthy women. Higher levels of AT in vWD-affected females, compared to controls, may also contribute to the existing bleeding tendency in this cohort.

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