Peri-operative desmopressin combined with pharmacokinetic-guided factor VIII concentrate in non-severe haemophilia A patients.

INTRODUCTION: Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated. AIM: We assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients. METHODS: Non-severe, desmopressin responsive, haemophilia A patients were included in one of two studies investigating peri-operative combination treatment. In the single-arm DAVID study intravenous desmopressin (0.3 µg/kg) once-a-day was, after sampling, immediately followed by PK-guided FVIII concentrate, for maximally three consecutive days. The Little DAVID study was a randomized trial in patients undergoing a minor medical procedure, whom received either PK-guided combination treatment (intervention arm) or PK-guided FVIII concentrate only (standard arm) up to 2 days. Dose predictions were considered accurate if the absolute difference between predicted and measured FVIII:C was ≤0.2 IU/mL. RESULTS: In total 32 patients (33 procedures) were included. In the DAVID study (n = 21), of the FVIII:C trough levels 73.7% (14/19) were predicted accurately on day 1 (D1), 76.5% (13/17) on D2. On D0, 61.9% (13/21) of peak FVIII:C levels predictions were accurate. In the Little DAVID study (n = 12), on D0 83.3% (5/6) FVIII:C peak levels for both study arms were predicted accurately. Combination treatment reduced preoperative FVIII concentrate use by 47% versus FVIII monotherapy. Desmopressin side effects were mild and transient. Two bleeds occurred, both despite FVIII:C > 1.00 IU/mL. CONCLUSION: Peri-operative combination treatment with desmopressin and PK-guided FVIII concentrate dosing in nonsevere haemophilia A is feasible, safe and reduces FVIII consumption.

Desmopressin, Misoprostol, nor Carboprost Affect Platelet Aggregability Following Traumatic Brain Injury and Aspirin.

INTRODUCTION: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA. METHODS: Male C57BL/6 mice were randomized into seven groups (n = 5 each): untouched, ASA only, Saline/TBI, ASA/TBI, ASA/TBI/DDAVP 0.4 µg/kg, ASA/TBI/misoprostol 1 mg/kg, and ASA/TBI/carboprost 100 µg/kg. TBI was induced via a weight drop model 4-h after ASA (50 mg/kg) gavage. Mice were given an intraperitoneal injection of DDAVP, misoprostol, or carboprost 10 minutes after TBI. In vivo testing was completed utilizing tail vein bleed. Mice were sacrificed 30-min posttreatment and blood was collected via cardiac puncture. Whole blood was analyzed via Multiplate impedance aggregometry, rotational thromboelastometry, and TEG6s. RESULTS: Mice receiving misoprostol after ASA/TBI demonstrated decreased tail vein bleeding times compared to ASA only treated mice. However, mice treated with misoprostol following ASA and TBI demonstrated decreased platelet aggregability compared to untouched mice and TBI only mice within the arachidonic acid agonist pathway. By contrast, DDAVP and carboprost did not significantly change platelet aggregability via adenosine diphosphate or arachidonic acid following ASA and TBI. However, DDAVP did decrease the platelet contribution to clot via rotational thromboelastometry. CONCLUSIONS: Reversal of medication-induced platelet inhibition has become increasingly controversial after TBI. Based on these results, DDAVP, misoprostol, nor carboprost consistently improve platelet aggregability following TBI in those also treated with ASA.

Effect of laser acupuncture on monosymptomatic nocturnal enuresis in adolescent females: A randomized controlled trial.

BACKGROUND AND AIM: Nocturnal enuresis (NE) is prevalent in children and adolescents and affects their social life later. Therefore, the objective of this study was to ascertain laser acupuncture (LA) therapy's effect on NE in adolescent females. METHODS: Sixty adolescent females diagnosed with chronic monosymptomatic nocturnal enuresis (MNE) were randomly divided into two equal groups: The intervention group (received LA and desmopressin) and the control group (received desmopressin only) (n = 30 each). Treatment was delivered and LA was used three times a week for 12 successive weeks. Abdominal ultrasonography and voiding calendar were used to assess bladder capacity and maximum voiding volume (MVV), respectively. The frequency of bed wetness was assessed throughout the trial period in a diary. RESULTS: Statistically significant differences were reported in the intervention group. Bladder capacity significantly increased in the intervention group (LA and desmopressin) than in the control group. CONCLUSIONS: The results of this study suggest the beneficial influences of LA on MNE, despite the very poor quality of the literature's available evidence.

Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: a systematic literature review.

BACKGROUND: Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVES: We aimed to review the safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

How I treat von Willebrand disorders in older adults.

ABSTRACT: von Willebrand disease (VWD) is the most common bleeding disorder and especially milder type 1 VWD might not be cared for in specialty clinics. VW factor levels rise with age, but the rise of these levels does not necessarily correlate with bleeding risk. A recent bleeding history combined with recent labs are important for hemostatic management decision during surgical interventions. Antifibrinolytics appear safe in the population of older adults, whereas desmopressin (DDAVP) should be used cautiously. Where needed, factor concentrates present a great treatment option. Acquired von Willebrand syndrome is vastly underrecognized, but likely to surface in the aging, especially in the setting of comorbidities, such as plasma-cell dyscrasias. Intravenous immunoglobulin can be an effective treatment in this scenario, but potentially increases thrombotic risk.

Unravelling the effect of blood group on FVIII:C levels and response to DDAVP in 20 males with a single genotype (Twillingate Variant) causing Haemophilia A.

INTRODUCTION: The genetic variant responsible for haemophilia A (HA) significantly impacts endogenous coagulant factor VIII (FVIII:C) level, thus impacting DDAVP responsiveness. Blood group (BG) also impacts FVIII:C levels, but this is difficult to evaluate in a genetically heterogeneous population. Canada has a large cohort of mild-moderate HA due to a single point variant: c.6104T>C, p.Val2035Ala-the Twillingate variant. AIM: To evaluate the impact of BG on endogenous FVIII:C levels and DDAVP responsiveness in a single genotype of mild-moderate HA. METHODS: This was a retrospective, single-centre study. BG and FVIII:C levels were obtained for males with the Twillingate variant. One-hour absolute and fold increases in FVIII:C post-DDAVP were calculated. T-tests and Mann-Whitney U tests were used to compare FVIII:C levels and DDAVP challenge variables between individuals according to BGs (O vs. non-O). RESULTS: Twenty males were included. There were significant differences between BGs (O vs. non-O) in their lowest FVIII:C level at age <12 years (medians: 0.05 vs. 0.08 IU/mL; P = .05). Fifteen subjects underwent DDAVP challenges. Mean 1-h FVIII:C were 0.29 (O BG) versus 0.41 IU/mL (non-O BG); P = .04. There were no significant differences between BGs (O vs. non-O) in mean absolute FVIII:C increase (0.20 vs. 0.27 IU/mL; P = .10) and FVIII:C fold increase (3.3-fold vs. 3.8-fold; P = .51). CONCLUSION: In HA subjects with an identical genotype, BG significantly impacts baseline FVIII:C levels and FVIII:C levels post-DDAVP, but does not impact absolute and fold increases in FVIII:C with DDAVP.

Incidence of postoperative hyponatremia after endoscopic endonasal pituitary transposition for skull base pathologies.

PURPOSE: Pituitary transposition is a novel surgical approach to access the retroinfundibular space and interpeduncular cistern. Few studies have evaluated post-surgical outcomes, including incidence of hyponatremia, following pituitary transposition. METHODS: This is a retrospective study including 72 patients who underwent endoscopic endonasal surgery involving pituitary transposition for non-pituitary derived tumors over a decade at the University of Pittsburgh Medical Center. Anterior pituitary deficiencies and replacement therapy, tumor pathology and pre-operative serum sodium (Na) were recorded. Na was assessed at postoperative day 1, 3, 5, 7, and 10. Anatomical/surgical parameters included sellar height, sellar access angle to approach the tumor, and cranial extension of the tumor above the sellar floor (B) compared to the height of the gland (A) (B/A). T-test (normally distributed variables) and Wilcoxon rank-sum test (not-normally distributed) were applied for mean comparison. Logistic regression analyzed correlations between anatomical/surgical parameters and postoperative hyponatremia. RESULTS: 55.6% of patients developed post-operative transient hyponatremia. Two patients (5%) developed severe hyponatremia (sodium level < 120 mmol/L). Eleven (15.3%) patients required desmopressin replacement immediately post-operatively, and 2 other patients needed desmopressin after discharge and after sodium nadir developed. Hyponatremia was inversely associated with sellar access angle (p = 0.02) and the tumor cranial extension above the sellar floor showing a trend towards significance (p = 0.09). CONCLUSION: More than half of patients who had pituitary transposition developed transient hyponatremia. Hyponatremia was more common in those with narrower sellar access angle and smaller cranial extension of the tumor above the sellar floor. Anatomical/surgical parameters may allow risk-stratification for post-operative hyponatremia following pituitary transposition.

Comparison of add-on medications for persistent storage symptoms after α-blocker treatment in BPH patients - a network meta-analysis.

BACKGROUND: Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, ß3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, ß3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients. METHODS: A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome. RESULTS: A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition. CONCLUSIONS: BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications.

Effect of Multidisciplinary Assessment on Paediatric Patients with Monosymptomatic Nocturnal Enuresis.

OBJECTIVE: This study aimed to investigate the effect of multidisciplinary assessment in paediatric patients with monosymptomatic nocturnal enuresis (MNE). METHODS: From July 2018 to June 2021, 242 patients with enuresis who received diagnosis and treatment in our hospital were retrospectively enrolled. They were divided into the multidisciplinary assessment group (n = 130) and routine assessment group (n = 112). Multidisciplinary assessments were completed by a multidisciplinary team, and the data included structured medical history, physical and neurological examinations, bladder and bowel diaries, sleep diaries, questionnaires, psychological assessments, urinary ultrasonography, blood and urine laboratory tests, polysomnography and balance assessments. RESULTS: A higher proportion of patients with enuresis associated with other conditions was identified in the multidisciplinary assessment group than in the routine assessment group (27.7% vs 15.2%, p = 0.019). With regard to treatment response to the enuresis alarm, the treatment response rate was 52.9% (17/33) in the conventional assessment group, whereas such a response was significantly higher in the multidisciplinary assessment group (82.1%, 32/39; p = 0.028). Compared with the routine assessment group, the multidisciplinary assessment group had a significantly higher treatment response rate for desmopressin (83.3% vs 52.0%; p = 0.022) and alarms combined with desmopressin (74.2% vs 44.4%; p = 0.045). After treatment, the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) score in the multidisciplinary assessment group was significantly higher than that in the routine assessment group (91.9 ± 6.3 vs 87.1 ± 7.3; p < 0.001). CONCLUSIONS: Multidisciplinary evaluation can identify more children with enuresis caused by other diseases, which promotes the differential diagnosis of MNE. In addition, multidisciplinary assessment can determine the appropriate treatment response in children with MNE.

Management of treatment-resistant nocturnal enuresis.

Nocturnal enuresis is defined as intermittent urinary incontinence during sleep in children 5 years of age and older, occurring at least once a month for at least 3 months. In Japan, pediatricians who do not specialize in nocturnal enuresis have become more proactive in treating the condition since 2016, when the guidelines for treating it were revised for the first time in 12 years. For monosymptomatic nocturnal enuresis, the first step is lifestyle guidance, with a focus on the restriction of fluid intake at night; however, if lifestyle guidance does not decrease the frequency of nocturnal enuresis, aggressive treatment should be added. The first choice of aggressive treatment is oral desmopressin, an antidiuretic hormone preparation, or alarm therapy. However, there remain patients whose wet nights do not decrease with oral desmopressin or alarm therapy. In such cases, it is necessary to reconfirm the method of desmopressin administration and check for factors that may decrease the efficacy of desmopressin. If alarm therapy does not increase the number of dry nights, it is possible that the patient is fundamentally unsuitable for alarm therapy. If dry nights do not increase with oral desmopressin or alarm therapy, the next treatment strategy should be considered immediately to keep the patient motivated for treatment.

Desmopressin (DDAVP) use in patients with von Willebrand disease: A single-centre retrospective review of test response and clinical outcomes.

INTRODUCTION: Peri-procedural management of von Willebrand disease (VWD) utilizes von Willebrand factor (VWF) concentrates or desmopressin (DDAVP) to increase VWF levels. DDAVP is safe, easily administered, and inexpensive. Currently, a consensus definition for adequate DDAVP response is lacking, and outcomes of peri-procedural DDAVP use in VWD patients are seldom reported. AIM: This single-centre retrospective review aims to characterize DDAVP-responsiveness and assess clinical outcomes of peri-procedural DDAVP use in VWD. PATIENTS AND METHODS: We reviewed records for all our adult VWD patients (age ≥18 years) who underwent DDAVP challenge testing between January 2007 and January 2022. DDAVP-responsiveness was assessed using six definitions. Bleeding outcomes following procedures covered by DDAVP were classified as excessive or expected bleeding. RESULTS: Eighty-four of 94 (89.4%) patients were DDAVP-responsive by our definition (1-h VWF Activity/Factor VIII ≥0.50 IU/mL). However, the proportion of DDAVP-responders varied from 53.2% to 91.5%, depending on the literature definition used. Ninety-nine procedures pre-treated with DDAVP were performed during the study period. Eighty-six (86.7%) procedures (31 major; 55 minor) were covered with only DDAVP ± tranexamic acid (TXA). Excessive bleeding occurred following 4/31 major procedures and 2/55 minor procedures (both performed in a single patient with a bleeding score of 16). When covered with DDAVP+Factor ± TXA, one each of 10 major and 3 minor procedures (performed in 2 patients with bleeding scores 15-16) resulted in post-procedural bleeding. CONCLUSIONS: Peri-procedural DDAVP prophylaxis appears to be effective among individuals with VWD. Beyond DDAVP-responsiveness, patient bleeding history and procedure invasiveness should be considered in determining suitability for DDAVP prophylaxis.

Initial outcomes using a novel bedwetting alarm (Gogoband®) that utilizes real time artificial intelligence to wake users prior to wetting.

We evaluated a new bedwetting alarm, GOGOband®® which utilizes real time heart rate variability (HRV) analysis and applied artificial intelligence (AI) to create an alarm that can wake the user prior to wetting. Our aim was to evaluate the efficacy of GOGOband® for users in the first 18-months of use. METHODS: A quality assurance study was conducted on data retrieved from our servers, of initial users of the GOGOband® which includes a heart rate monitor, moisture sensor, bedside PC-tablet, and a parent app. There are three sequential modes beginning with Training, Predictive mode and Weaning mode. Outcomes were reviewed and data analysis was done with SPSS and xlstat. RESULTS: All 54 subjects who used the system from Jan 1, 2020, to June 2021 for more than 30 nights were included in this analysis. The mean age of the subjects is 10.1 ± 3.7 yrs. Subjects wet the bed a median of 7 (IQR6-7) nights per week prior to treatment. Severity and number of accidents per night had no impact on the ability to achieve dryness with GOGOband®. A crosstab analysis was performed which indicated that high compliant users (>80%) can remain dry 93% of the time compared to the whole group 87.7%. Overall ability to achieve 14 dry nights in a row was 66.7% (36/54) with some achieving a median of 16 14-day periods of dryness (IQR 0-35.75). CONCLUSIONS: We found 93% dry night rate in high compliance users in Weaning, this translates to 1.2 wet nights per 30 days. This compares to all users who wet 26.5 nights prior to treatment and 11.3 wet nights per 30 days during Training. The ability to achieve 14 days straight of dry nights was 85%. Our findings indicate that GOGOband® provides a significant benefit to all its users reducing nocturnal enuresis rates.

Desmopressin Plus Tolterodine vs Desmopressin Plus Indomethacin for Refractory Pediatric Enuresis: An Open-label Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of desmopressin plus tolterodine (D+T) with desmopressin plus indomethacin (D+I) for treating enuresis in children. DESIGN: Open-label randomized controlled trial. SETTING: Bandar Abbas Children's Hospital, a tertiary care children's hospital in Iran, from March 21, 2018, to March 21, 2019. PARTICIPANTS: 40 children older than five years with monosymp-tomatic and non-monosymptomatic primary enuresis resistant to desmopressin monotherapy. INTERVENTION: Patients were randomized to receive either D+T (60 µg sublingual desmopressin and 2 mg tolterodine) or D+I (60 µg sublingual desmopressin and 50 mg indomethacin) every night before bedtime for five months. OUTCOME: Reduction in the frequency of enuresis was evaluated at one, three, and five months, and response to treatment at five months. Drug reactions and complications were also noted. RESULTS: After adjustment for age, consistent incontinence from toilet training, and non-monosymptomatic enuresis, D+T was significantly more efficacious than D+I; mean (SD) percent in nocturnal enuresis reduction at 1 [58.86 (7.27)% vs 31.18 (3.85) %; P<0.001], 3 [69.78 (5.99) % vs 38.56 (3.31) %; P<0.000], and 5 [84.84(6.21) % vs 39.14 (3.63) %; P<0.001] months showing a large effect. At 5 months, complete response to treatment was only observed with D+T, while treatment failure was significantly higher with D+I (50% vs 20%; P=0.047). None of the patients in either group developed cutaneous drug reactions or central nervous system symptoms. CONCLUSION: Desmopressin plus tolterodine appears to be superior to desmopressin plus indomethacin for treating pediatric enuresis resistant to desmopressin.

Comparative Analysis of Solifenacin Plus Desmopressin Versus Desmopressin Alone in the Treatment of Primary Mono Symptomatic Nocturnal Enuresis.

OBJECTIVES: To compare the efficacy and tolerability of Solifenacin plus Desmopressin and Desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis (PMNE). METHODS: A total of 88 children, 5-14 years old, diagnosed with PMNE were enrolled in this randomized control trial (RCT) from June 2017 to June 2020. After informed written consent patients were randomized to one of the two therapeutic groups. Group 1 received one puff of desmopressin nasal spray 1 h before bedtime every night. Group 2 received one pill of solifenacin 5 mg plus one puff of desmopressin nasal spray 1 h before bedtime every night. All patients were evaluated after three months for their response to treatment and drug side effects. RESULTS: The mean age in desmopressin alone group and solifenacin plus desmopressin group was 8.1 ± 2.2 (5-14) and 7.9 ± 2.2 (5-14) years respectively (p-value >0.05). In group 2, 37/44 (84.09%) patients achieved complete response after three months of treatment in comparison to group 1 in which 27/44 (61.36%) patients showed complete response (p-value <0.05). In group 1, 8/44 (18.18%) patients developed treatment related side effects whereas in group 2, 12/44 (27.27%) patients developed side effects (p-value >0.05). No case of discontinuation of treatment due to side effects was observed in any of the two groups. The recurrence rate was also significantly lower in group 2 in comparison to group 1 (8.1% vs 33.3%, p-value <0.05). CONCLUSION: Our study demonstrated that the combination of Solifenacin plus Desmopressin is more effective than desmopressin monotherapy in the treatment of PMNE with an acceptable tolerability profile. LEVEL OF EVIDENCE: Level I.

Eficácia E Custo-Utilidade De Intervenções Para O Tratamento Da Enurese Em Crianças E Adolescentes Sob A Perspectiva Do Sistema Único De Saúde Brasileiro: Effectiveness and Cost-Utility of Interventions for Enuresis Treatment in Children and Adolescents From the Brazilian Single Health System Perspective.

OBJECTIVES: This study aimed to estimate the cost-utility of effective interventions for enuresis treatment in children and adolescents and to calculate the incremental cost-utility ratio from the perspective of the Brazilian Unified Health System in a 1-year time horizon. METHODS: The economic analysis is in 7 stages: (1) survey of evidence of treatments for enuresis, (2) performing the network meta-analysis, (3) estimation of the probability of cure, (4) cost-utility analysis, (5) model sensitivity analysis, (6) analysis of acceptability of interventions by acceptability curve, and (7) monitoring the technological horizon. RESULTS: The association between desmopressin and oxybutynin is the therapeutic strategy with the highest probability of success in the treatment of enuresis in children and adolescents compared with placebo (relative risk [RR] 2.88; 95% confidence interval [CI] 1.65-5.04), followed by the combination therapy between desmopressin and tolterodine (RR 2.13; 95% CI 1.13-4.02), alarm (RR 1.59; 95% CI 1.14-2.23), and neurostimulation (RR 1.43; 95% CI 1.04-1.96). Combination therapy between desmopressin and tolterodine was the only 1 considered not to be cost-effective. Neurostimulation, alarm therapy, and therapy had the respective incremental cost-utility ratio values: R$5931.68, R$7982.92, and R$29 050.56/quality-adjusted life-years. CONCLUSION: Among the therapies that are on the borderline of efficiency, the combined therapy between desmopressin and oxybutynin presents the greatest incremental benefit at an incremental cost that is still feasible, given that it does not exceed the reference value of the cost-effectiveness threshold established in Brazil.

Drugs to reduce bleeding and transfusion in major open vascular or endovascular surgery: a systematic review and network meta-analysis.

BACKGROUND: Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion. OBJECTIVES: To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss. SEARCH METHODS: We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes. AUTHORS' CONCLUSIONS: Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.