Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties.
We aimed to review the safety and effectiveness of ...DDAVP in women with an inherited bleeding disorder during pregnancy and delivery.
Databases were searched for articles up to July 25, 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology for systematic reviews and meta-analyses was followed (PROSPERO CRD42022316490).
Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 women during pregnancy and in 232 during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse events reported in 2 (1%, hyponatremia with neurologic symptoms). Overall, DDAVP was used as monotherapy in 234 pregnancies, with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, 2 children (3%) had a severe adverse event (preterm delivery n = 1; fetal growth restriction n = 1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery, and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n = 1; transient hyperbilirubinemia not associated with DDAVP n = 1).
DDAVP use during pregnancy and delivery seems safe for the mother, with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.
Desmopressin causes two- to six-fold increase of factor VIII (FVIII) in mild or moderate haemophilia A patients. However, responses are variable and little is known whether this is associated with F8 ...gene mutation. The study objective was to assess the relationship between F8 gene mutation and desmopressin response in haemophilia A patients. Desmopressin response (absolute and relative) was determined in 97 hemophilia A patients. Four amino acid changes (Arg2169His, Pro149Arg, Asn637Ser, and Arg612Cys) and a number of other mutations leading to an aberrant FVIII protein or FVIII deficiency were analysed. Patients with Arg2169His showed significantly lower FVIII levels before and after desmopressin compared to all other mutations (p<0.001). Pro149Arg amino acid change showed significantly lower FVIII levels 1 hour after desmopressin compared to all other mutations (p<0.005). An absolute response with FVIII≥0.50 IU/ml after 1 hour was observed in 41% (9 of 22) of patients with Arg2169His; however, this was not sustainable after 6 hours in any of these subjects. No patients with Pro149Arg mutation (n=6) showed an absolute response with FVIII≥0.50 I U/ml. Patients with other mutations showed significantly more complete and partial responses. Relative responses did not differ between mutations. Our study shows that haemophilia A patients with amino acid change Arg2169His or Pro149Arg have a decreased desmopressin response with regard to FVIII levels as compared to other mutations. Our results indicate that response to desmopressin is dependent on the F8 gene mutation type, despite the fact that multiple factors influence the desmopressin response, even within families.
BACKGROUNDThe recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging ...testing in patients with clinically suspected pulmonary embolism (PE).AIMTo externally validate the performance of 4PEPS in an independent cohort.METHODSIn this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer <1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold.RESULTSOf the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80-0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57-60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86-1.9).CONCLUSIONIn this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.
Essentials
Statins, especially rosuvastatin, may reduce venous thrombosis risk, but the mechanism is unclear.
We performed a randomized trial investigating the effect of rosuvastatin on platelet ...reactivity.
Thromboxane‐A2 mediated platelet aggregation was measured before and after rosuvastatin therapy.
Rosuvastatin did not inhibit thromboxane‐mediated platelet aggregation in venous thrombosis patients.
Summary
Background
Statins may exert a protective effect against the risk of venous thrombosis (VT), but the mechanism is unclear.
Objectives
In this open‐label, randomized clinical trial (www.clinicaltrials.gov NCT01613794), we aimed to determine the ex vivo effect of rosuvastatin on platelet reactivity in patients with a history of VT.
Methods
Platelet reactivity, in platelet reaction units (PRUs), was measured at baseline and after 28 days with VerifyNow, which uses arachidonic acid to determine thromboxane‐mediated platelet aggregation, in 50 consecutive patients included in our study (25 receiving rosuvastatin and 25 without intervention).
Results
Forty‐seven of 50 (94.0%) consecutively enrolled patients had two valid PRU measurements. The mean PRUs in rosuvastatin users were 609 at baseline and 613 at the end of the study (mean change 5; 95% confidence interval CI − 18 to 27). The mean PRUs in non‐users were 620 at baseline and 618 at the end of the study (mean change − 2; 95% CI − 15 to 12). The mean difference in PRU change between users and non‐users was 6 (95% CI − 20 to 33). After exclusion of patients who used antiplatelet medication, or had thrombocytopenia, similar results were obtained, i.e. no apparent effect of rosuvastatin on PRUs, with a mean difference in PRU change between users and non‐users of − 1 (95% CI − 20 to 19).
Conclusions
Rosuvastatin does not affect platelet reactivity when arachidonic acid is used as an agonist in patients with a history of VT.
In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% ...of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.
This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs).
A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.
A total of 3,148 outpatient VKA users were included, with a mean age (standard deviation) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol, and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic (odds ratio OR = 1.34 95% confidence interval CI 1.08-1.67) and subtherapeutic levels (OR = 1.40 95% CI 1.08-1.83) after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination (OR = 2.29 95% CI 1.22-4.28) and 3.3 times higher after second vaccination (OR = 3.25 95% CI 1.06-9.97).
BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with VKAs, so it is advisable to monitor the INR shortly after vaccination, even in stable patients.
The most optimal management for patients with bleeding of unknown cause (BUC) is unknown, as limited data are available.
Evaluate management and outcome of surgical procedures and deliveries in ...patients with BUC.
All patients ≥12 years of age, referred to a tertiary center for a bleeding tendency, were included. Bleeding phenotype was assessed and hemostatic laboratory work-up was performed. Patients were diagnosed with BUC or an established bleeding disorder (BD). Data on bleeding and treatment during surgical procedures and delivery following diagnosis were collected.
Of 380 included patients, 228 (60%) were diagnosed with BUC and 152 (40%) with an established BD. In 14/72 (19%) surgical procedures major bleeding occurred and 14/41 (34%) deliveries were complicated by major postpartum hemorrhage (PPH). More specifically, 29/53 (55%) of the BUC patients who underwent surgery received prophylactic treatment to support hemostasis. Despite these precautions, 4/29 (14%) experienced major bleeding. Of BUC patients not treated prophylactically, bleeding occurred in 6/24 (25%). Of pregnant women with BUC, 2/26 (8%) received prophylactic treatment during delivery, one women with and 11 (46%) women without treatment developed major PPH.
Bleeding complications are frequent in BUC patients, irrespective of pre- or perioperative hemostatic treatment. We recommend a low-threshold approach toward administration of hemostatic treatment in BUC patients, especially during delivery.
Background
Anticoagulant therapy is associated with a high risk of complications. Adherence to anticoagulant therapy protocols may lower this risk but adherence is often suboptimal. The introduction ...of a multidisciplinary antithrombotic team may improve adherence to anticoagulant guidelines among physicians.
Objective
To determine the effect of hospital-based multidisciplinary antithrombotic stewardship on adherence to anticoagulant guidelines among prescribing physicians.
Setting
This prospective non-randomised before-and-after study was conducted in patients hospitalized between October 2015 and December 2017 and treated with anticoagulant therapy.
Method
A multidisciplinary antithrombotic team focusing on education, medication reviews, drafting of local anticoagulant therapy protocols, patient counseling and medication reconciliation at admission and discharge was implemented in two Dutch hospitals.
Main outcome measure
Primary outcome was the proportion of the admitted patients in which the prescribing physician did adhere to the anticoagulant guidelines.
Results
The study comprised 1886 patients, of which 941 patients were included in the usual care period and 945 patients in the intervention period. Multivariable logistic regression analysis indicated that adherence was observed significantly more often during the intervention period (adjusted odds ratio ORadj 1.58, 95% confidence interval 95% CI 1.21–2.05). Detailed analysis identified that the significantly higher overall adherence in the intervention period was attributed to dosing of LMWHs (odds ratio OR 1.58, 95% CI 1.16–2.14).
Conclusion
This study shows that introduction of a multidisciplinary antithrombotic stewardship leads to a significantly higher overall adherence to anticoagulant guidelines among prescribing physicians, mainly based on the improvement of dosing of low-molecular-weight-heparins.
Summary
Essentials
Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins.
FVII‐induced International Normalized Ratio (INR) changes differ between commercial ...reagents.
Recombinant human thromboplastins are more sensitive to FVII than tissue‐extract thromboplastins.
Thromboplastin choice may affect FVII‐mediated INR stability.
Summary
Background
Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue‐extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs).
Objectives
To determine whether commercial thromboplastins react differently to changes in FVII.
Methods
We studied the effect of addition of FVII on the INR in plasma by using three tissue‐extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL−1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5–3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents.
Results
After addition of 0.062 μg mL−1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose‐dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue‐extract thromboplastins. Pooled results indicated that the FVII‐induced INR change was greater for recombinant than for tissue‐extract thromboplastins.
Conclusions
Differences regarding FVII sensitivity exist between various thromboplastins used for VKA monitoring. Recombinant human thromboplastins are more sensitive to FVII than tissue‐extract thromboplastins. Therefore, thromboplastin choice may affect FVII‐mediated INR stability.
Phenotypic characterization of congenital platelet defects (CPDs) could help physicians recognize CPD subtypes and can inform on prognostic implications. We report the analyses of the bleeding ...phenotype and diagnostic characteristics of a large cohort of adult patients with a confirmed CPD. A total of 96 patients were analyzed and they were classified as Glanzmann thrombasthenia, Bernard‐Soulier syndrome, dense granule deficiency, defects in the ADP or thromboxane A2 (TxA2) pathway, isolated thrombocytopenia or complex abnormalities. The median ISTH‐BAT bleeding score was nine (IQR 5‐13). Heavy menstrual bleeding (HMB) (80%), post‐partum hemorrhage (74%), post‐operative bleeds (64%) and post‐dental extraction bleeds (57%) occurred most frequently. Rare bleeding symptoms were bleeds from the urinary tract (4%) and central nervous system (CNS) bleeds (2%). Domains with a large proportion of severe bleeds were CNS bleeding, HMB and post‐dental extraction bleeding. Glanzmann thrombasthenia and female sex were associated with a more severe bleeding phenotype.
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