| 1. |
- Armstrong, Elina, et al.
(författare)
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Assay discrepancy in mild haemophilia A
- 2014
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Ingår i: European Journal of Haematology. Supplementum. - : Wiley. - 0902-4506 .- 0902-4441. ; 93:s76, s. 48-50
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Forskningsöversikt (refereegranskat)abstract
- UNLABELLED: There are three main methods used to assay factor VIII (FVIII) activity: the one-stage and two-stage clotting assays and the two-stage chromogenic method. The most commonly used assay for the diagnosis of haemophilia A is the automated one-stage FVIII assay. The classical two-stage FVIII assays are less frequently used. The chromogenic FVIII:C assay is a variant of the two-stage assay. It is easier to use and therefore used more commonly. Recently significant assay discrepancy has been recognised in the FVIII:C measurements in approximately one-third of mild haemophilia A patients. This so-called discrepant mild haemophilia A is characterised by a high ratio of one-stage/two-stage assay with one-stage FVIII levels that are typically more than double those of the two-stage coagulation assay. There are several mutations that destabilise the FVIIIa structure that can explain this result of a more pronounced decrease of the chromogenic FVIII:C activity compared with the one-stage activity. These mutations are clustered at the interfaces of the A1, A2 and A3 domains of the FVIII protein. The inverse discrepancy, where the one-stage assay gives lower FVIII:C results than the chromogenic assay, seems to be associated with mutations found close to important sites for thrombin cleavage or FIX binding. We are carrying out a study of mild haemophilia A samples from the Malmö Haemophilia Centre of families with a unique F8 genotype. The activity of FVIII will be measured using a chromogenic assay and two different one-stage assays. We hope to estimate the true size of assay discrepancy.AIM: This project will review assay discrepancy in mild/moderate haemophilia A and the risk of misdiagnosis. The overall aim is to estimate the size of the problem and to learn from the literature and experiences from our centre as well as to suggest recommendations on how to avoid misdiagnosis.
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| 2. |
- Lassila, Riitta, et al.
(författare)
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Practical Viewpoints on the Diagnosis and Management of Heparin-Induced Thrombocytopenia
- 2011
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 37:3, s. 328-335
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-induced thrombocytopenia (HIT, type II) is an immune-mediated disorder due to antibodies formed against heparin platelet factor 4 complexes, usually appearing at days 5 to 14 after initiation of heparin. It is important to recognize HIT because heparin prophylaxis or treatment paradoxically associates with new venous and/or arterial thrombosis. Early clinical suspicion and diagnosis together with proper pharmacotherapy and close laboratory monitoring are the cornerstones for successful management. This includes monitoring of Thrombocytopenia, its Timing to heparin administration, appearance of new Thrombosis or resistance to treatment, and differential diagnosis by exclusion of oTher causes (the 4T's). Specific attention should be paid to the absence or presence of thrombosis and to tailoring thromboprophylaxis or anticoagulant therapy with a nonheparin alternative. Even in the absence of HIT-associated thrombosis, an active policy for prolonged thromboprophylaxis is demanded. Rapid and reliable assays should be developed for diagnosis and anticoagulation monitoring to secure safe management with nonheparins. Semiquantitative testing for on-call hours should be available and later confirmed as clinically needed. Alternative therapeutic options are available, but because their use is infrequent, experienced coagulation treatment centers should provide guidance in the treatment and in laboratory monitoring. Most of the evidence in HIT is grade IC, and thus the best evidence is provided by clinical experience. New anticoagulants and platelet inhibitors may offer future alternatives in the management of HIT, but the current treatment options provide the best experience and benefit. The joint clinical and laboratory guidelines provided in this article along with two practical case scenarios were prepared by a Nordic expert panel. They will be valuable for hematologists and colleagues who do not routinely encounter HIT.
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| 3. |
- Tyrrell, Jessica, et al.
(författare)
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Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
- 2016
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
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Tidskriftsartikel (refereegranskat)abstract
- Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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