Impact of antithrombotic agents on outcomes in patients requiring surgery for chronic subdural haematoma: a systematic review and meta-analysis.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

Standardization of definition and management for bleeding disorder of unknown cause: communication from the SSC of the ISTH.

In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool. Patients with increased bleeding assessment tool scores should progress to hemostasis laboratory testing. To diagnose bleeding disorder of unknown cause (BDUC), normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function, coagulation factors VIII, IX, and XI, and platelet light transmission aggregometry should be the minimum laboratory assessment. In some laboratories, additional specialized hemostasis testing may be performed to identify other rare causes of bleeding. We recommend that patients with a significant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of BDUC in preference to other terminology. Global hemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical significance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for BDUC patients include tranexamic acid, desmopressin, and platelet transfusions.

A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease.

BACKGROUND: For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens. METHODS: This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period. RESULTS: Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients. CONCLUSION: This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings.

D-dimer Release From Livers During Ex Situ Normothermic Perfusion and After In Situ Normothermic Regional Perfusion: Evidence for Occult Fibrin Burden Associated With Adverse Transplant Outcomes and Cholangiopathy.

BACKGROUND: Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are because of peribiliary vascular fibrin microthrombi. We sought to determine the prevalence and consequence of occult fibrin within deceased donor livers undergoing normothermic ex situ perfusion (NESLiP) and evaluate a role for fibrinolysis. METHODS: D-dimer concentrations, products of fibrin degradation, were assayed in the perfusate of 163 livers taken after 2 h of NESLiP, including 91 that were transplanted. These were related to posttransplant outcomes. Five different fibrinolytic protocols during NESLiP using alteplase were evaluated, and the transplant outcomes of these alteplase-treated livers were reviewed. RESULTS: Perfusate D-dimer concentrations were lowest in livers recovered using in situ normothermic regional perfusion and highest in alteplase-treated livers. D-dimer release from donation after brain death livers was significantly correlated with the duration of cold ischemia. In non-alteplase-treated livers, Cox proportional hazards regression analysis showed that D-dimer levels were associated with transplant survival ( P = 0.005). Treatment with alteplase and fresh frozen plasma during NESLiP was associated with significantly more D-dimer release into the perfusate and was not associated with excess bleeding postimplantation; 8 of the 9 treated livers were free of cholangiopathy, whereas the ninth had a proximal duct stricture. CONCLUSIONS: Fibrin is present in many livers during cold storage and is associated with poor posttransplant outcomes. The amount of D-dimer released after fibrinolytic treatment indicates a significant occult fibrin burden and suggests that fibrinolytic therapy during NESLiP may be a promising therapeutic intervention.

Long-term risk of relapse in immune-mediated thrombotic thrombocytopenic purpura and the role of anti-CD20 therapy.

Disease relapse is recognized as a risk in immune-mediated thrombotic thrombocytopenic purpura (iTTP) after treatment of the acute presenting episode. Identification of patients at risk of relapse and its patterns are yet to be clearly established. We reviewed patients with iTTP having had >3 years of follow-up over 10 years in the United Kingdom to identify patient characteristics for relapse, assess relapse rates and patterns, and response to anti-CD20 therapy in those with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) relapses (ADAMTS13 activity of <20% without thrombocytopenia). We identified 443 patients demonstrating relapse rates of 40% at 5-year follow-up. At 10-year follow-up, no difference in relapse was observed irrespective of whether rituximab was used at acute presentation (P = .39). Black Caribbean ethnicity increased the risk of disease relapse in the British population. There was a distinct population of patients (6%) that relapsed early with subsequent frequent relapses occurring on average within 2 years (average time to relapse in subgroup, 1.7 years). Overall, nearly 60% of relapses described were ADAMTS13 relapses, with subsequent treatment reducing the risk of progression to clinical relapses. We demonstrate that iTTP diagnosed in the latter part of the study period had lower rates of clinical relapses (22.6% vs 11.1%, P = .0004) with the advent of regular monitoring and preemptive rituximab. In ADAMTS13 relapses, 96% responded to anti-CD20 therapy, achieving ADAMTS13 activity of >20%. Anti-CD20 therapy was demonstrated to be an effective long-term treatment regardless of relapse pattern and there was no loss of this treatment response after subsequent treatment episodes.

Outcomes and management of pregnancy in women with bleeding disorder of unknown cause.

BACKGROUND: Patients with a bleeding tendency with normal laboratory tests have been described as having an unclassified bleeding disorder or bleeding disorder of unknown cause (BDUC). There are very little data available on how to manage pregnancy. OBJECTIVES: To study management and outcomes of these patients at four United Kingdom hemophilia comprehensive care centers. METHODS: Retrospective case note review from 2010-2020. RESULTS: Sixty deliveries in 36 patients were recorded. The median International Society on Thrombosis and Haemostasis bleeding assessment tool score was 9. In 54 cases for which data were available, the odds ratio for post partum hemorrhage (PPH) was 6.3 for no primary hemostatic prophylaxis versus prophylaxis (95% confidence interval 1.2-34.2, p < .05); 7/9 (78%) versus 16/45 (36%) PPH incidence for the groups, respectively. Hemostatic prophylaxis was with tranexamic acid but some patients received desmopressin or platelet infusions. Secondary PPH was seen in 5/60 (8%) of cases. No neonatal bleeding complications or maternal thromboembolic complications were noted. Avoidance of regional anesthesia and fetal delivery precautions were commonly advised, but in the small number of cases in which they occurred no complications were noted. CONCLUSIONS: Despite hemostatic prophylaxis PPH was commonly seen. Further prospective studies of BDUC patients are required to determine optimal management in pregnancy as well as determine the pathophysiological basis of bleeding.

Severe refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab.

A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293 units/L and bilirubin of 228 µmol/L, refractory to standard treatment with corticosteroids and rituximab. An emergency splenectomy was performed that slowed haemolysis but did not completely ameliorate it. Eculizumab, a terminal complement pathway inhibitor, was initiated to arrest intravascular haemolysis and showed a favourable response. AIHA is rare but described after the SARS-CoV-2 Pfizer-BioNTech vaccine. This case highlights the rare complication of AIHA, the use of emergency splenectomy for disease control, and the use of eculizumab.

The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura.

Rituximab, an anti-CD20 monoclonal antibody, can be used to treat immune thrombotic thrombocytopenic purpura (iTTP) during acute presentation or disease relapse. Undesirable side-effects include severe hypersensitivity reactions, particularly anaphylaxis and rituximab-induced serum sickness, with a minority not maintaining a response to treatment. Alternative humanised anti-CD20 treatments, obinutuzumab and ofatumumab, have been used. A review of the UK TTP Registry showed 15 patients received these drugs over 26 treatment episodes (eight obinutuzumab and 18 ofatumumab). Indications for alternative anti-CD20 treatment were severe infusion-related reactions, acute rituximab-induced serum sickness and a short duration of disease remission. All patients achieved disease remission (ADAMTS13 [A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] activity ≥30 iu/dl) after a median 15 days and 92% of episodes achieved complete remission (≥60 iu/dl). Seven patients required further treatment for disease relapse with a median relapse-free survival of 17.4 months. All patients continued to respond to re-treatment with the preceding drug when relapse occurred. There were four adverse events in 26 treatment episodes (15%) - two infections and two infusion reactions. These results suggest that obinutuzumab and ofatumumab may be considered as an alternative option to rituximab in the treatment of iTTP with a comparable safety profile, absence of significant hypersensitivity reactions and sustained normalisation of ADAMTS13.

Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis.

The COVID-19 pandemic has resulted in the rapid development of a range of vaccines against SARS-CoV-2. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare but life-threatening complication of primarily adenoviral-based vaccines associated with the presence of antibodies to a PF4/polyanion neoepitope and measured by using enzyme-linked immunosorbent assays. Presented are serial anti-PF4/polyanion antibody, platelet, and D-dimer measurements in a large cohort of patients and their relation to relapse. Overall, 51% of patients using the Stago assay had persistently positive anti-PF4/polyanion levels 100 days' postdiagnosis, whereas 94% of patients monitored by using the Immucor assay remain positive. The median duration of positivity of the PF4 assay is 87 days, with 72% of patients remaining positive after a median follow-up of 105 days. The use of plasma exchange seemed to reduce anti-PF4/polyanion levels and increase platelet counts in the acute setting more rapidly than other therapies. The rate of relapse in this study was 12.6%, with all relapsed cases exhibiting persistently positive PF4 antibodies and falling platelet counts. Only one patient had extension of their thrombosis. Overall, despite the persistence of PF4 antibodies in 72% of patients, the rate of relapse was low and did not seem to result in recrudescence of the aggressive clinical picture seen at index presentation. Monitoring of these patients in the UK cohort is ongoing and will aid in definition of the natural history of this novel condition.

Direct oral anticoagulants-Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitors.

BACKGROUND: The optimal method of detecting a lupus anticoagulant (LA) for patients taking direct factor Xa inhibitor (DFXaI) direct oral anticoagulants (DOACs) remains controversial. Methods include charcoal adsorption of the DOACs to allow testing with the activated partial thromboplastin time (APTT) and dilute Russell viper venom time (dRVVT), or use of the DFXaI-insensitive Taipan snake venom time (TSVT) and Ecarin time (ET) assays on neat plasma. OBJECTIVES: The objective was to compare the utility of APTT and dRVVT analysis following DOAC Remove against TSVT/ET on untreated plasma for LA detection in spiked plasmas and routine clinical samples for patients on DFXaIs. PATIENTS/METHODS: Various LA-negative and LA-positive samples were assayed by APTT, dRVVT, and TSVT/ET, and then separately spiked with rivaroxaban, apixaban, and edoxaban calibrators to a concentration of ~190 ng/ml and the assays repeated on spiked plasma before and after DOAC Remove treatment. Testing of 284 consecutive samples from DFXaI-anticoagulated patients by APTT/dRVVT and TSVT/ET before and after DOAC Remove treatment was undertaken. RESULTS: In the spiking model, we found that both TSVT/ET and DOAC Remove strategies generally distinguished LA-negative and LA-positive samples, but some false-positive LA results occurred. In the investigation of 284 consecutive patient samples on DFXaIs, the percentage agreement for LA detection in neat samples tested by TSVT/ET versus APTT and dRVVT after DOAC Remove treatment was 90% (Cohen kappa 0.12). CONCLUSION: Our data highlight uncertainty and disagreement for testing LA in patients on DFXaI. Further studies are required.

Current practice and registration patterns among United Kingdom Haemophilia Centre Doctors' Organisation centers for patients with unclassified bleeding disorders.

BACKGROUND: Bleeding of unknown cause (BUC) and unclassified bleeding disorders (UBD) are increasingly recognized. There is no guidance on diagnosis and management. OBJECTIVES: To examine UK haemophilia centre registration patterns and current practice for UBD patients. METHODS: In a two-step process, the UK National Haemophilia Database (NHD) was reviewed for registration patterns of UBD patients and a survey of UK haemophilia centers was conducted (January/February 2021) to capture current practice for diagnosis and management of patients with UBD. RESULTS/DISCUSSION: Overall, registrations with the NHD for UBD patients has sharply risen from 2012 to 2020 and in 2019 accounted for 2.65% of registered patients. For the survey, the response rate was 52/67 (78%). Practice was widely variable; 35/52 (67%) centers register UBD; among these 35 centers, terminology included UBD (28 centers), undiagnosed bleeding disorder (four centers), and BUC (three centers); 34/52 (65%) centers use a formal bleeding assessment tool. For management of dental extraction and high bleeding risk surgery in a fictional UBD patient we found that tranexamic acid was widely used; however, beyond this a variety of hemostatic products were advised including blood products, recombinant factor VIIa/prothrombin complex concentrate, and desmopressin. There was general consensus (≈90%) on avoiding regional anesthesia in pregnancy, but no agreement on the need for fetal precautions to avoid bleeding at delivery (50% would advise these). There was a disparity of opinion on chemical thromboprophylaxis, and management of patients without prior hemostatic challenges and offspring of these patients. CONCLUSION: This study provides a snapshot of current practice and real-world data in this area. Future studies need to address the gaps in evidence.

Investigation of platelet function in patients with chronic kidney disease stages IV-V.

INTRODUCTION: Patients with renal failure are at increased risk of both bleeding and thrombosis. Further descriptions of laboratory investigations in these patients are required. METHODS: Investigation of 24 patients with chronic kidney disease (CKD) stages IV-V with light transmission aggregometry, platelet secretion assays and platelet nucleotide analysis. Patients were in a nonbleeding state and not on antiplatelet medication. Results were compared with our local reference range used within the clinical haematology service. RESULTS: Of the 24 patients, two had decreased responses to arachidonic acid, adenosine diphosphate, collagen, thrombin receptor activator peptide-6 and one had decreased responses to high dose ristocetin, and one had increased response to low dose ristocetin. 11 and 13 out of 24 had abnormal platelet secretion release to collagen and thrombin, respectively. Platelet nucleotide analysis in patients was normal with the exception of a reduction in ADP content in one patient and ATP/ADP ratio in one patient. CONCLUSIONS: In our collection of patients with CKD investigated for platelet function in the nonbleeding state, they generally had normal light transmission aggregometry and nucleotide analysis but around 50% had decreased platelet secretion assays. These results could be important in determining the significance of platelet function tests in patients with bleeding symptoms and renal failure. Further characterization of platelet function tests in future will help characterize haemostasis in renal failure further.

International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

BACKGROUND: Lupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin-activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI). OBJECTIVES: Validate standardized TSVT/ET reagents for LA detection, in a multicenter, multiplatform study. PATIENTS/METHODS: Six centers from four countries analyzed samples with TSVT/ET from 81 nonanticoagulated patients with LA, patients with established antiphospholipid syndrome (APS), and proven persistent LA who were either not anticoagulated (n = 120) or were anticoagulated with VKAs (n = 180) or DFXaIs (n = 71). Additionally, 339 nonanticoagulated LA-negative patients, and 575 anticoagulated non-APS patients (172 VKA, 403 DFXaI) were tested. Anticoagulant spiking experiments were performed and 112 samples containing potential interferences (i.e., direct thrombin inhibitors) were tested. Results were evaluated against locally derived cutoffs. Imprecision was evaluated. RESULTS: Cutoffs were remarkably similar despite use of different analyzers and donor populations. Cutoffs for TSVT ratio, ET ratio, percent correction, and normalized TSVT ratio/ET ratio ranged between 1.08 and 1.10, 1.09 and 1.12, 9.3% and 14.8%, and 1.10 and 1.15, respectively. Coefficients of variation for TSVT and ET ratios were ≤5.0%. TSVT/ET exhibited sensitivity, specificity, and negative and positive predictive values of 78.2%/95.0%/86.3%/91.5%, respectively, with established APS as the LA-positive population, and 86.9%/95.0%/76.8%/97.4%, respectively, with triple-positive APS. Interference was seen with direct thrombin inhibitors, unfractionated heparin, and low molecular weight heparins, but not VKAs or DFXaIs. CONCLUSIONS: TSVT/ET are validated for LA detection in nonanticoagulated patients and those on VKAs or DFXaIs.

Transplant-associated thrombotic microangiopathy and immune haematological complications following intestine-containing organ transplantation: experience from over 100 consecutive cases.

Descriptions of passenger lymphocyte syndrome (PLS), immune cytopenias and transplant-associated thrombotic microangiopathy (TA-TMA) after intestine-containing transplants remain scarce. We describe our centre's experience of these complications from 2007 to 2019. Ninety-six patients received 103 transplants. PLS occurred in 9 (9%) patients (median 12 days post-transplant); all due to ABO antibodies. There were 31 minor ABO mismatch transplants. No patient required change in immunosuppression. Immune cytopenias (excluding PLS) occurred in six patients at an incidence of 1·7/100 patient years; three immune haemolysis, one immune thrombocytopenia, one acquired Glanzmann's and one immune neutropenia; 50% occurred with other cytopenias. All cases eventually responded to treatment, with a median of four treatments (range 1-8) and 5/6 were treated with rituximab. One patient with immune haemolysis required bortezomib. Complications were common in patients with immune cytopenias; 4/6 with infection needing intravenous antibiotics and 3/6 with venous thromboembolism. In 3/6 cases, a secondary cause for the immune cytopenia was evident. Switching from tacrolimus to ciclosporin was not necessary. There were five cases of transplant-associated thrombotic microangiopathy (TA-TMA; 1·5/100 patient years) requiring calcineurin inhibitor withdrawal; two cases associated with acute rejection. Two cases were managed with plasma exchange, one with plasma infusions and one with eculizumab. Further research in this patient group is required.

Understanding good leadership in the context of English care home inspection reports.

PURPOSE: As part of their inspection of care homes in England, the statutory inspector (the Care Quality Commission [CQC]) makes a judgement on the quality of the home's leadership. Their view is critical as it is intended to inform consumer choice and because the statutory nature of inspection means these views hold considerable authority. The purpose of this paper is to look at the content of a selection of reports and seek to determine what the CQC understands by the concept of "good leadership". DESIGN/METHODOLOGY/APPROACH: A purposive sample of recent CQC inspection reports was selected and subjected to a qualitative content analysis. Inspections are structured around five main questions. The resulting themes describe areas of focus within the section of reports that feature the question "Are they well-led?". FINDINGS: Inspection reports were found to focus on four main themes: safety and quality of care; day-to-day management of staff; governance and training in the home; and integration and partnership working. In the discussion section, the authors reflect on these themes and suggest that the CQC's view of leadership is rather limited. In particular, while an emphasis is placed within the literature and policy on the importance of leadership in delivering change and quality improvement, little attention is paid to this within the leadership section of inspection reports. RESEARCH LIMITATIONS/IMPLICATIONS: The authors' research is based on a small-scale sample of inspection reports; nevertheless, it suggests a number of avenues for further research into the way in which leadership and management capabilities are developed and monitored in the sector. ORIGINALITY/VALUE: The analysis in this report offers a view of how the inspection regime implements its own guidance and how it assesses leadership. The reports, as public-facing documents, are artefacts of the inspection regime and critical not just as evidence of the practice of inspection but as influence on care home operations and the choices of care home residents and their families.

Management of surgery, menorrhagia and child-birth for patients with unclassified bleeding disorders: a systematic review of cohort studies.

Unclassified bleeding disorders account for 2.6% of all new bleeding disorder registrations in the UK. The management of the bleeding phenotype associated with these disorders is poorly described. Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid, desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII, for patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia. We searched for randomized controlled trials in MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science and the Transfusion Evidence Library from inception to 24 February 2020. Wherever appropriate, data were pooled using the metaprop function of STATA. Two studies with 157 participants with unclassified bleeding disorders were identified. The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative tranexamic acid was 11% (95% confidence interval 3--20%; n = 52; I2 = 0%); the risk for desmopressin and tranexamic acid in combination was 3% (95% confidence interval 0--7%; n = 71; I2 = 0%). There were no instances of major bleeding. In one procedure, 1 of 71 (1.4%), treated with a combination of desmopressin and tranexamic acid, the patient had a line-related deep vein thrombosis. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia to draw conclusions. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both tranexamic acid, and the combination of tranexamic and desmopressin have high rates of haemostatic efficacy and have few adverse events. PROTOCOL REGISTRATION: PROSPERO CRD42020169727.