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Featured researches published by M. Holmström.


Haemophilia | 2013

Incidence, mortality rates and causes of deaths in haemophilia patients in Sweden.

Susanna Lövdahl; Karin M. Henriksson; Fariba Baghaei; M. Holmström; J.-Å. Nilsson; Erik Berntorp; Jan Astermark

Sweden has been a pioneer in the treatment of haemophilia, with the first concentrate available in the 1950s. Treatment has improved over the years to its current state‐of‐the art. The aim of the current study was to evaluate the long‐term outcome of haemophilia in terms of incidence, morbidity and mortality. Patients diagnosed with haemophilia A or B registered at the national haemophilia centres and/or the Patient Registry and born before 2009 and alive in 1968 were enrolled and linked to the Cause of Death‐, Migration‐ and Medical Birth registries. Five age‐ and sex‐matched controls were selected for each patient. A total of 1431 patients with haemophilia A or B were compared with 7150 controls. The 3‐year moving average incidence rate per 100 000 population varied between 21 and 36. The hazard ratio for all‐cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001 and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates.


Haemophilia | 2012

Combined treatment with APCC (FEIBA®) and tranexamic acid in patients with haemophilia A with inhibitors and in patients with acquired haemophilia A – a two‐centre experience

M. Holmström; H. T. T. Tran; P. A. Holme

Summary.  The management of bleeding in haemophilia patients with inhibitors can be challenging when using monotherapy with either activated prothrombin complex concentrate (APCC) or recombinant activated FVII (rFVIIa) fail. The antifibrinolytic agent tranexamic acid (TXA) increases clot stability and is used concomitantly with coagulation factor replacement to improve haemostasis in haemophilia patients without inhibitors in many countries in Europe. Combined treatment with TXA and rFVIIa is not contraindicated in haemophlia patients with inhibitors. However, the combined approach of TXA and APCC has not been investigated due to safety concerns of increased risk of thrombosis or disseminated intravasal coagulation (DIC). The aim of this study is to report our experience of concomitant use of APCC and TXA in haemophilia A patients with inhibitor and in patients with acquired haemophilia A with respect to safety and efficacy. Seven (n = 6) haemophilia A patients with inhibitors and one (n = 1) with acquired haemophilia A from Oslo (Norway) and Stockholm (Sweden) were included in the study. The APCC was given at doses consistent to the manufacturers’ recommendation. TXA was administered concomitantly either 10 mg kg−1 every 6–8 h intravenously or 20 mg kg−1 every 6–8 h orally. Haemostatic response was assessed by thromboelastography (TEG) and thrombin generation assay (TGA) in three of the patients. A total number of three bleeding episodes and two minor and six major surgical procedures were performed under the coverage with APCC and TXA. Haemostatic outcome was rated excellent or good in 10 of 11 (91%) treatment episodes. One episode was rated with poor effect. No episodes of arterial, venous thrombosis or DIC occurred during or after the treatment. Data from TEG and TGA analysis showed no signs of hypercoagulability following the combined treatment. This report demonstrates that, in a limited number of patients, combined treatment with APCC and TXA seemed to be safe, tolerated and relatively effective in management of bleeding episodes and in preventing haemorrhage during surgery in haemophilia patients with inhibitors and in a patient with acquired haemophilia A. Further studies should be performed to confirm these data.


Haemophilia | 2012

Treatment of haemophilia A and B and von Willebrand's disease: summary and conclusions of a systematic review as part of a Swedish health-technology assessment.

Erik Berntorp; Jan Astermark; Fariba Baghaei; David Bergqvist; M. Holmström; Bengt Ljungberg; Anders Norlund; J Palmblad; P Petrini; L. Stigendal; Juliette Säwe

Summary.  In an ongoing health‐technology assessment of haemophilia treatment in Sweden, performed by the governmental agency Dental and Pharmaceutical Benefits Agency (TLV; tandva˚rds‐och lākemedelsförma˚nsverket), the Swedish Council on Health Technology Assessment (SBU; statens beredning för medicinsk utvārdering) was called upon to evaluate treatment of haemophilia A and B and von Willebrand’s disease (VWD) with clotting factor concentrates. To evaluate the following questions: What are the short‐term and long‐term effects of different treatment strategies? What methods are available to treat haemophilia patients that have developed inhibitors against factor concentrates? Based on the questions addressed by the project, a systematic database search was conducted in PubMed, NHSEED, Cochrane Library, EMBASE and other relevant databases. The literature search covered all studies in the field published from 1985 up to the spring of 2010. In most instances, the scientific evidence is insufficient for the questions raised in the review. Concentrates of coagulation factors have good haemostatic effects on acute bleeding and surgical intervention in haemophilia A and B and VWD, but conclusions cannot be drawn about possible differences in the effects of different dosing strategies for acute bleeding and surgery. Prophylaxis initiated at a young age can prevent future joint damage in persons with haemophilia. The available treatment options for inhibitors have been insufficiently assessed. The economic consequences of various treatment regimens have been insufficiently analysed. Introduction of national and international registries is important.


Journal of Thrombosis and Haemostasis | 2017

Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations

J.I. Loomans; A.S. van Velzen; C.L. Eckhardt; M. Peters; Anne Mäkipernaa; M. Holmström; Paul P. T. Brons; Natasja Dors; Saturnino Haya; Jan Voorberg; J. G. van der Bom; Karin Fijnvandraat

Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter‐individual variation in factor VIII levels. Intra‐individual variation accounted for 45% of the variation in the three largest mutation groups.


Haemophilia | 2017

A prospective diagnostic accuracy study evaluating rotational thromboelastometry and thromboelastography in 100 patients with von Willebrand disease.

David E. Schmidt; Ammar Majeed; Maria Bruzelius; Jacob Odeberg; M. Holmström; Anna Ågren

Rotational thromboelastometry (ROTEM®) and thromboelastography (TEG®) are increasingly used in the perioperative and emergency assessment of bleeding tendencies. The diagnostic value of ROTEM and TEG for von Willebrand disease (VWD) remains to be established.


Haemophilia | 2015

Bleeding phenotype in carriers of haemophilia A does not correlate with thrombin generation

Anna Olsson; M. Hellgren; Erik Berntorp; M. Holmström; Fariba Baghaei

A. OLSSON,* M. HELLGREN,†‡ E. BERNTORP,§ M. HOLMSTR € OM¶ and F. BAGHAEI* *Department of Haematology and Coagulation Disorders, Sahlgrenska University Hospital, Gothenburg; †Department of Antenatal Care N€arh€alsan Primary Care, V€astra G€ otaland; ‡Department of Obstetrics and Gynaecology Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg; §Centre for Thrombosis and Haemostasis Sk ane University Hospital, Lund University, Malm€ o; and ¶Coagulation Unit Haematology Centre, Karolinska University Hospital, Stockholm, Sweden


Haemophilia | 2017

Comparative burden of arthropathy in mild haemophilia: a register‐based study in Sweden

Mehdi Osooli; S. Lövdahl; K. Steen Carlsson; K. Knobe; Fariba Baghaei; M. Holmström; Jan Astermark; Erik Berntorp

Mild haemophilia is a congenital bleeding disorder affecting males. The burden of arthropathy in mild haemophilia has not been comprehensively described.


Haemophilia | 2014

A longitudinal study of family structure in Swedish persons with haemophilia.

Susanna Lövdahl; Karin M. Henriksson; Fariba Baghaei; M. Holmström; Erik Berntorp; Jan Astermark

Haemophilia is an X‐linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age‐ and gender‐matched controls. The national Multi‐Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.


Haemophilia | 2016

Long-term liver-related morbidity and mortality related to chronic hepatitis C virus infection in Swedish patients with inherited bleeding disorders

M. Holmström; A. Nangarhari; J. Öhman; Ann-Sofi Duberg; A. Majeed; Soo Aleman

Hepatitis C virus (HCV) infection is common in patients with inherited bleeding disorders treated with clotting factor concentrates prior to the introduction of viral inactivation of these products. The long‐term consequences of hepatitis C infection in Swedish patients are not fully understood.


Haemophilia | 2014

Clinical presentation of inhibitor development in non-severe hemophilia A: Half of patients have high titer inhibitors and present with bleeding complications

Corien L. Eckhardt; Janneke I. Loomans; Alice S. Van Velzen; Marjolein Peters; Jan Astermark; Paul P. T. Brons; Giancarlo Castaman; Marjon H. Cnossen; Natasja Dors; Carmen Escuriola-Ettingshausen; Karly Hamulyak; Daniel P. Hart; C. R. M. Hay; Saturnino Haya; Waander L. van Heerde; Cédric Hermans; M. Holmström; Victor J. Imenez-Yuste; Russell Keenan; R. Klamroth; Britta A.P. Van Laros-Gorkom; Frank W.G. Leebeek; Ri Liesner; Anne Mäkipernaa; Christoph Male; E. P. Mauser-Bunschoten; Maria Gabriella Mazzucconi; Simon McRae; Karina Meijer; Michael Mitchell

Category: Communication Models. Objective(s): The objective of this activity was to increase international awareness of girls and women with bleeding disorders by creating a collection of interesting videos and sharing them through social media. Methods: Women attending several bleeding disorder conferences were given an opportunity to participate in a video activity. Permission forms were obtained from each woman. Several video themes were used to capture information. Some women provided a brief self-introduction. Another video shows a woman holding up posters telling about the signs and symptoms of bleeding and where to find a hemophilia treatment center anywhere in the world. Several videos are groups of girls and women who are dancing and waving. The videos were edited and posted on the MyGirlsBlood Facebook and website. A compilation of the women’s introductions was posted on the World Federation of Hemophilia Facebook page in support of World Hemophilia Day. Results: The statistics below are from November, 2012 – October, 2013: There are over 25 videos created in this collection. There were 6,563 viewings across 46 countries. Top counts were: United States (4,609), India (627), Poland (200), Israel (110), Canada (131), Taiwan (113), China (163), United Kingdom (124), Spain (87), and Argentina (40). Conclusion: Providing video(s) of women with bleeding disorders, the signs and symptoms of bleeding and fun videos all help provide awareness throughout the world of bleeding disorders found in girls and women. Contribution to the Practice/Evidence base of Hemophilia and Bleeding Disorders: The majority of social media, videos and educational materials in the bleeding disorder community are related to boys and men. Materials created directly for women and shared on social networking sites will provide continued growth of the knowledge library of our women’s community. Pregnancy management in inherited bleeding disorders MARIA V INOGRADOVA , ROMAN SHMAKOV , TAT IANA FEDOROVA , EUGEN IA POLUSHK INA and OLEG ROGACHEVSKY Federal Scientific Centre for Obstetrics, Gynecology and Perinatology, Moscow, Russia Introduction and Objectives: In recent years the quality of life of patients with several inherited bleeding disorders (IBD) has improved considerably due to implementation of new medicines as well as the optimization of diagnostic approaches. For this reason the issues of reproductive health with respect to these patients are becoming very important. Early diagnosis, pregnancy planning and establishment of protocols for management of pregnancy and delivery are crucial to their quality of life. Our multidisciplinary team has been optimizing strategy for the management of pregnant patients with IBD. Materials and Methods: Since 2010 we have analyzed 31 pregnancies in 28 women with IBD: 18 with von Willebrand disease (VWD), three carriers of hemophilia A, seven patients with partial deficiency of clotting factors (CF): FI, FVII, FXI, FX. All of them underwent monitoring and preventive treatment when necessary. In VWD, we used the DDAVP and the CF concentrate containing VWF until the levels of CF were above 50 IU/ml. In cases of other CF deficiencies we prescribed the fresh frozen plasma. Recombinant FVIIa has been used to cover Caesarean section and postpartum hemorrhage (PPH). Results: Spontaneous miscarriage has been observed in two (6,5%) patients. No neonatal mortality has occurred. We detected IBD in three newborns. No bleeding events were registered during pregnancy. Most women with type 1 VWD and moderate forms of FVII deficiency, developed an increase of CF levels as a physiological response to pregnancy. Only two (6,9%) cases required regular treatment throughout pregnancy. Therapy administration was based on the mother’s factor levels. Caesarean sections were administered in 12(38,7%) births. We observed the intraoperative hemorrhage in one case (3,4%) of placenta previa, secondary PPH in 3(10,3%) cases. Intracranial hemorrhage has been diagnosed in 3 neonates. Conclusion: The risk of hemorrhagic complications during pregnancy and postpartum in IBD may be minimized by applying of the management algorithm with preventive treatment. For women with low factor levels preventive treatment with CF concentrates is necessary. Women with IBD need clinical vigilance during puerperium. Umbilical cord blood should be taken to measure CF levels in the newborn for prompt diagnosis of IBD. The Self-BAT (Self-administered Bleeding Assessment Tool) is an effective screening tool for von Willebrand disease in women referred to hematology MEGHAN DEFOREST , 1 JUL IE GRABELL , 1 WILMA HOPMAN and PAULA JAMES 1 Queen’s University, Kingston, Canada The value of standardized, quantitative bleeding scores (BS) has been recognized in the assessment of hemorrhagic symptoms, particularly when used as a screening tool to identify patients in need of laboratory testing. Most BATs (bleeding assessment tools) are expert administered; we developed the Self-BAT by converting the ISTHBAT (International Society on Thrombosis and Haemostasis) into lay language and optimized it by studying individuals previously known to have Type 1 VWD and healthy controls. After revision, the Intraclass Correlation Coefficient of Self-BAT BS and ISTH-BAT BS was high at 0.869. The objective of the current study is to test the diagnostic utility of the Self-BAT as a screening tool for women referred to hematology for the first time for a possible bleeding disorder. Female subjects over the age of 18 were recruited in the hematology clinic. Subjects were ineligible if they had a previous diagnosis of a bleeding disorder, were pregnant or had an acquired cause of bleeding (ie: medications, renal or hepatic disease). After informed consent, subjects were provided the Self-BAT and asked to complete it, without assistance, prior to the appointment. BSs were calculated using the 0 to +4 scoring system. Blood was drawn for CBC, ferritin, ABO, VWF:Ag, VWF:RCo and FVIII. To date, 22 females have been enrolled. Subject characteristics can be found in Table 1. Nineteen had a positive or abnormal BS (≥5) and of those five had laboratory results consistent with Type 1 VWD. Therefore, the sensitivity =100%, specificity=18%, positive predictive value=0.26, negative predictive value=1.0. Additional testing of those without VWD (including platelet aggregometry and platelet dense granule quantitation) is ongoing. In conclusion, our preliminary data strongly suggest that the Self-BAT is an effective screening tool to incorporate into the hematologic assessment of women referred for a possible bleeding disorder. VWD (n=5) No VWD (n=17) P value

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Paul P. T. Brons

Radboud University Nijmegen

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Anne Mäkipernaa

Helsinki University Central Hospital

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Fariba Baghaei

Sahlgrenska University Hospital

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Marjolein Peters

Boston Children's Hospital

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Russell Keenan

Boston Children's Hospital

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