von Willebrand disease (VWD) is the most common inherited bleeding disorder known in humans. Accurate and timely diagnosis presents numerous challenges.
These evidence-based guidelines of the ...American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and other health care professionals in their decisions about VWD diagnosis.
ASH, ISTH, NHF, and WFH established a multidisciplinary guideline panel that included 4 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Outcomes and Implementation Research Unit at the University of Kansas Medical Center (KUMC) supported the guideline-development process, including performing or updating systematic evidence reviews up to 8 January 2020. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subsequently subject to public comment.
The panel agreed on 11 recommendations.
Key recommendations of these guidelines include the role of bleeding-assessment tools in the assessment of patients suspected of VWD, diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD, how to approach a type 1 VWD patient with normalized levels over time, and the role of genetic testing vs phenotypic assays for types 2B and 2N. Future critical research priorities are also identified.
Individual risk of recurrent venous thromboembolism affects patient management and might differ between men and women. We did a meta-analysis to assess from available evidence whether men and women ...have the same risk of recurrent venous thromboembolism after stopping anticoagulant treatment.
Eligible articles were identified by searches of MEDLINE (source PubMed, 1966 to February 2005), EMBase (1980 to February 2005), and the Cochrane database 2005, issue 1. Prospective cohort studies and randomised trials were eligible if they included patients with objectively diagnosed venous thromboembolism treated for a minimum of 1 month and followed up for recurrence after anticoagulant treatment was stopped. Data were extracted for study design, study quality, and the number, sex, and age of enrolled patients, risk factors for venous thromboembolism, treatment given, duration of follow-up, and the number of episodes of recurrent venous thrombosis.
15 studies (nine randomised controlled trials and six prospective observational studies) enrolling a total of 5416 individuals (2729 men), of whom 816 (523 men) had recurrent venous thromboembolism after stopping treatment, were eligible for inclusion. The pooled estimate of the relative risk (RR) of recurrent venous thromboembolism for men compared with for women was 1·6 (95% CI 1·2–2·0). Significant heterogeneity was shown among individual study findings; however, the higher risk of recurrent venous thromboembolism in men than in women was consistent across predefined subgroups. The relative risk for recurrence in men from randomised trials (RR 1·3; 95% CI 1·0–1·8) was lower than that from observational studies (2·1; 1·5–2·9). The lower risk of recurrent venous thromboembolism in women did not seem to be accounted for by a reduced rate of recurrence after venous thromboembolism associated with oestrogen treatment or pregnancy.
Men seem to have a 50% higher risk than women of recurrent venous thromboembolism after stopping anticoagulant treatment. If confirmed by further prospective studies, this difference in risk of recurrence should be considered when duration of anticoagulant treatment is determined in individual patients.
In recent years, there has been greater awareness among hemostasis scientists and clinicians that factor VIII coagulant activity (FVIII:C) measured in certain patients with mild hemophilia A can show ...different results depending on the assay system. A subgroup of mild hemophilia families have a method-related discrepancy in FVIII:C results, whereby the one-stage clotting assay (FVIII:C-1) is significantly higher than the two-stage clotting assay (FVIII:C-2) or the chromogenic assay (FVIII:C-chr). To identify such patients, the routine laboratory can use automated procedures for the FVIII:C-chr to replace the complex, manual FVIII:C-2 method. Laboratories must employ appropriate quality management to ensure accurate and precise results, especially in the abnormal range. This discrepant phenotype of hemophilia A is seen in up to 40% of mild hemophilia A cases and represents a clinically significant bleeding disorder. A small proportion of these cases have FVIII:C-1 within the normal range and risk a missed diagnosis if the FVIII:C-chr is unavailable. Other patients may be mismanaged if FVIII:C-1 gives an overestimate of FVIII:C and their bleeding risk is consequently underestimated. Affected family members in the discrepant group of patients have a limited range of FVIII (F8) gene missense mutations, causing alterations of the structure of the A1, A2, or A3 domains of FVIII. Therefore, both FVIII:C-chr and F8 gene mutation analysis are recommended to confirm the diagnosis of mild hemophilia A and assist with decisions about the patient's phenotype.
Intravenous fluids may contribute to lower haemoglobin levels in patients with septic shock. We sought to determine the relationship between the changes in haemoglobin concentration and the volume of ...intravenous fluids administered during resuscitation from septic shock.
We performed a retrospective cohort study of patients enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial who were not transfused red blood cells (N = 1275). We determined the relationship between haemoglobin concentration, its change over time and volume of intravenous fluids administered over 6, 24 and 72 h using univariate and multivariate analysis.
Median (IQR) haemoglobin concentration at baseline was 133 (118-146) g/L and decreased to 115 (102-127) g/L within the first 6 h of resuscitation (P < 0.001), 110 (99-122) g/L after 24 h, and 109 (97-121) g/L after 72 h. At the corresponding time points, the cumulative volume of intravenous fluid administered was 1.3 (0.7-2.2) L, 2.9 (1.8-4.3) L and 4.6 (2.7-7.1) L. Haemoglobin concentration and its change from baseline had an independent but weak association with intravenous fluid volume at each time point (R
< 20%, P < 0.001). After adjusting for covariates, each litre of intravenous fluid administered was associated with a change in haemoglobin concentration of - 1.0 g/L (95% CI -1.5 to -0.6, P < 0.001) at 24 h and - 1.3 g/L (- 1.6 to - 0.9, P < 0.001) at 72 h.
Haemoglobin concentration decreases during resuscitation from septic shock, and has a significant but weak association with the volume of intravenous fluids administered.
Background
Up to 65% of patients with myelodysplastic syndromes (MDS) have thrombocytopenia and require platelet (PLT) transfusion. The current standard of practice is to provide random‐ or ...single‐donor PLT transfusion and manage PLT refractoriness (PLT‐R) if and when it develops. This study assessed the prevalence and risk factors for immune‐mediated PLT‐R in patients in the South Australian (SA) MDS Registry.
Study Design and Methods
A retrospective analysis of MDS patients enrolled in the SA‐MDS registry was performed. HLA data was analyzed from January 2003 to 30 June 2017 to ensure minimum follow‐up of 2 years.
Results
During the study period, 341 of 681 (50%) MDS patients required at least one PLT transfusion, with 29 of 341 (9%) of all PLT transfusion patients requiring HLA‐matched PLT transfusion for PLT‐R. Of these 29 patients, 70% were females treated with disease‐modifying therapies suggesting that these patients are at high risk of HLA alloimmunization.
Conclusions
Immune‐mediated PLT‐R is common in MDS and can be expensive and difficult to manage once it occurs. Therefore, PLT transfusion practices should be optimized, especially for female MDS patients planned for disease‐modifying therapies. This can help save time and streamline management, especially in the provision of PLT products for these patients, where the consequences of alloimmunization and PLT‐R can be severe.
See editorial on page 2164–2167, in this issue
The prothrombotic risk in multiple myeloma (MM) could be potentially assessed by thrombin generation (TG) assays. TG was performed using Calibrated Automated Thrombography with 5 and 1 pM tissue ...factor. We compared baseline TG among 24 MM patients, 19 MGUS, and 50 healthy controls, and assessed change in TG in MM patients during the initial treatment period at 1, 2, and 3 months. MM subjects demonstrated increased FVIII and VWF:Ag levels pretreatment, and a prothrombotic TG phenotype with increased velocity index, reduced lag time and time-to-peak, and increased resistance to thrombomodulin inhibition. There were no significant changes in TG with treatment for the majority of parameters, however, MM subjects exhibited persistent elevation of velocity index throughout treatment. Two subjects developed thrombosis during the study period despite thromboprophylaxis. This study provides information on the optimal conditions for examining TG as a predictor of thrombotic risk in MM patients.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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•Immunothrombosis is believed to be the primary underlying mechanism for the coagulopathy associated with COVID-19.•A complex interplay between the immune system, endothelium and ...coagulation system, results in a hypercoagulable state.•D dimer has been shown to be the most reliable predictor of disease severity, thrombosis, and overall survival.•Thrombotic complications including venous, arterial and microvascular are common in COVID-19 patients despite routine thromboprophylaxis.•Novel approaches to prevent thrombosis driven by a hyperimmune response beyond traditional anticoagulation strategies alone are warranted.
The coagulopathy of COVID-19 is characterised by significantly elevated D Dimer and fibrinogen, mild thrombocytopenia and a mildly prolonged PT/APTT. A high incidence of thrombotic complications occurs despite standard thromboprophylaxis. The evidence to date supports immunothrombosis as the underlying mechanism for this coagulopathy which is triggered by a hyperinflammatory response and endotheliopathy. A hypercoagulable state results from endothelial damage/activation, complement activation, platelet hyperactivity, release of Extracellular Neutrophil Traps, activation of the coagulation system and a “hypofibrinolytic” state. Significant cross-talk occurs between the innate/adaptive immune system, endothelium and the coagulation system. D dimer has been shown to be the most reliable predictor of disease severity, thrombosis, and overall survival. In this context, targeting pathways upstream of coagulation using novel or repurposed drugs alone or in combination with other anti-thrombotic agents may be a rational approach to prevent the mortality/morbidity due to COVID-19 associated coagulopathy.
Abstract Background There is minimal data on the influence of pre-analytical variables on the use of calibrated automated thrombography (CAT), to measure thrombin generation. Objectives To evaluate ...the impact of centrifugation methods, time after collection, and contact activation inhibition on the CAT assay performed using two commercial reagents. Methods and Results Six different methods of plasma separation were examined. Thrombin generation triggered by a 5 pM tissue factor reagent was not greatly affected by plasma separation method, with similar results obtained with all methods apart from single centrifugation and membrane filtration. Membrane filtration increased APTT and is not recommended. Extended double centrifugation at higher speed was required to minimise the impact of residual phospholipid with 1 pM tissue factor trigger, particularly with inhibition of contact activation. The effect of a delay of up to 24 hours in preparing plasma was assessed. No significant difference in results was observed among samples processed between 0.5 and 6 hours after blood collection into plastic Vacuette® tubes. The presence or absence of corn trypsin inhibitor had a significant impact on all parameters with 1 pM tissue factor trigger, with minor differences seen on Peak and ttPeak results using 5 pM tissue factor. Conclusions The impact of pre-analytical variables on thrombin generation results is dependent on the concentration of tissue factor in the trigger reagent used. Results with 1 pM tissue factor are particularly sensitive to centrifugation method and contact activation, and standardisation is required to allow large collaborative studies to be performed.
Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to ...diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low‐molecular‐weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once‐daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice‐daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation.
Initial treatment of venous thromboembolism McRae, Simon J; Ginsberg, Jeffrey S
Circulation (New York, N.Y.),
2004-Aug-31, 2004-08-31, 20040831, Letnik:
110, Številka:
9 Suppl 1
Journal Article
Recenzirano
Odprti dostop
Adequate initial anticoagulant therapy of deep venous thrombosis (DVT) is required to prevent thrombus growth and pulmonary embolism (PE). Intravenous unfractionated heparin (UFH) is being replaced ...by low-molecular-weight heparin (LMWH) as the anticoagulant of choice for initial treatment of venous thromboembolism (VTE). Both agents are relatively safe and effective when used to treat VTE, with LMWH suitable for outpatient therapy because of improved bioavailability and more predictable anticoagulant response. Serious potential complications of heparin therapy, such as heparin-induced thrombocytopenia (HIT) and osteoporosis, seem less common with LMWH. The potential for fetal harm and changes in maternal physiology complicate the treatment of VTE during pregnancy. Although systemic thrombolysis is used in patients with massive PE and in some patients with proximal DVT, controversy persists with respect to appropriate patient selection for this intervention.
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