Impact of Desmopressin ON HemaToma EXPANsion in Patients Presenting to the Emergency Department on Antiplatelet Therapy: DON'T EXPAND Study

doi:10.21203/rs.3.rs-4619324/v1

Download PDF

Research Article

Impact of Desmopressin ON HemaToma EXPANsion in Patients Presenting to the Emergency Department on Antiplatelet Therapy: DON'T EXPAND Study

https://doi.org/10.21203/rs.3.rs-4619324/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Introduction: Current guidelines state the effectiveness of desmopressin to reduce hematoma expansion in antiplatelet-related intracerebral hemorrhage (ICH) is uncertain. This study sought to determine if desmopressin decreased hematoma expansion in ICH patients on antiplatelet agents.

Methods: We conducted a multi-center, retrospective propensity-matched cohort study at 11 US emergency departments (ED) that participate in EMPHARM-NET. Adult patients ≥18 years with a primary diagnosis of spontaneous ICH on antiplatelets prior to admission from January 1, 2017 through May 1, 2021 were included. The primary endpoint was good or excellent hemostatic efficacy within the first 24 hours following ICH between patients that did and did not receive desmopressin. Brain imaging was reviewed using 3D-Slicer by blinded expert physicians.

Results: Overall, 1408 patients were evaluated for inclusion. A total of 324 patients were included, of which 13.8% (n=45) received desmopressin and 86.1% (n=279) did not. After propensity matching, 35 patients receive desmopressin compared to 140 controls. Baseline hematoma volume (27.6 mL vs. 2.1 mL) and was significantly higher in the desmopressin group. The primary endpoint of good or excellent hemostatic efficacy was similar between groups (74.3% desmopressin group vs. 85% control group, -10.7% [-28.1% to 6.7%]). There was no difference in secondary outcomes.

Conclusion: In this multicenter cohort, patients receiving desmopressin had higher baseline intraparenchymal hematoma volume, and did not appear to result in improved hemostatic efficacy relative to the control group. These results suggest against routine administration of desmopressin for antiplatelet-related ICH, though future study in a randomized trial design is necessary.

Intracerebral hemorrhage (ICH) is a devastating neurologic emergency resulting in significant morbidity and mortality.¹ ICH is frequently identified and treated in the emergency department (ED).¹ Hematoma expansion following ICH has been associated with death and disability.^2,3 A number of factors are associated with hematoma expansion, including the use of anticoagulant or antiplatelet agents, time from symptom onset to baseline imaging, and ICH volume.⁴

Antiplatelet agents (e.g., aspirin, clopidogrel) are widely available and commonly used in patients presenting with ICH.⁵ Antiplatelet agents may increase risk of hematoma expansion and the potential for worse outcomes.^5,6 While a number of therapeutic options have been studied for anticoagulant reversal, there is a paucity of evidence supporting reversal of antiplatelet therapies in the setting of ICH.⁷ Despite this limited evidence, consensus guidelines for the reversal of antithrombotic agents in spontaneous or traumatic ICH suggest the administration of desmopressin in patients taking antiplatelet agents (conditional recommendation, low quality of evidence).^1,8

Desmopressin is a vasopressin analog, which promotes platelet adhesion to the endothelium by increasing endothelial release of von Willebrand factor (vWF) and factor VIII. vWF, in turn, enhances platelet adhesion to collagen and may also bind to platelet glycoprotein IIb/IIIa receptors. Additionally, desmopressin enhances formation of procoagulant platelets and platelet-dependent thrombin generation.^7,9 Therefore, desmopressin may have the ability to overcome the platelet dysfunction associated with antiplatelet agents. To date most studies evaluating desmopressin for antiplatelet-related ICH have been of retrospective design with small sample sizes.^6,10–13 Only one randomized trial, with the primary outcome of feasibility of enrollment, has been conducted.¹⁴ Data supporting desmopressin in this setting have demonstrated mixed results and “real world” data are limited. Significant evidence gaps remain with respect to the safety and efficacy of desmopressin in antiplatelet-related ICH. The purpose of our study was to determine if desmopressin impacted hemostatic effectiveness in patients with antiplatelet-related ICH presenting to EDs across the United States. We hypothesized that there would be no difference in hemostatic effectiveness with or without desmopressin.

This was a multicenter, retrospective observational cohort study at 11 hospital EDs across the United States. Sites were participants in the Emergency Medicine PHARMacotherapy research NETwork (EMPHARM-NET). Adult patients ≥18 years of age with a primary diagnosis of ICH (classified as epidural hematoma, intraparenchymal hemorrhage, subdural hematoma, or subarachnoid hemorrhage) on at least one antiplatelet agent prior to admission from January 1, 2017 through May 1, 2021 were included. This study was approved by the institutional review board at each participating site.

Patients were excluded for the following reasons: no follow up head computed tomography (CT) within 24 hours of initial CT, previous enrollment in the study, pregnancy, transfer from outside hospital if time to intervention is greater than 12 hours, concurrent ischemic stroke, neurosurgical interventions within 12 hours of admission (excluding external ventricular drains), international normalized ratio (INR) of ≥1.7 secondary to non-anticoagulant related coagulopathy (e.g. end stage liver disease), no antiplatelet agent on home medication list, isolated traumatic brain injury, or missing information (e.g. unable to obtain baseline CT from outside hospital). Patients were identified using ICD 10 code I62.9 (non-traumatic ICH, unspecified).

Patients were dichotomized according to receipt of desmopressin or not. Baseline demographics were collected, including comorbid conditions, social history and baseline laboratory values and vital signs. Type of ICH (intraparenchymal, subdural, or subarachnoid) was collected and severity of illness scores. Hemostatic agents, blood products, and neurosurgical interventions were also collected. The primary endpoint was good or excellent hemostatic efficacy within the first 24 hours (± 6 hours) following ICH according to the Scientific and Standardization Subcommittee (SSC) on Control of Anticoagulation of the International Society on Thrombosis and Haemostasis (ISTH) proposed criteria to evaluate the hemostatic effectiveness of anticoagulant reversal in major bleeding management and previous research.^15,16 Good or excellent hemostatic efficacy was defined as ≤35% increase in hematoma size. Brain imaging was reviewed by expert physicians who were blinded to the desmopressin status and were quantified hematoma volumes using 3D-Slicer^©, a free, open-source software designed to quantify hematoma volume and other data.¹⁷ Training sessions were held with physician experts to ensure competency and uniformity in data collection. Secondary endpoints included the following: discharge modified Rankin Scale (mRS) score and National Institute of Health Stroke Scale (NIHSS) score, in-hospital and 30-day mortality. Adverse events (AEs) included thromboembolic events (ischemic stroke, myocardial infarction, or venous thromboembolism) within seven days and serum sodium nadir within three days.

Statistical Analysis

Descriptive statistics were used to characterize the study population and distribution of baseline variables, and ICH characteristics. Normality of continuous data was assessed using the Shapiro-Wilks test. Continuous parametric data was compared using the t-test and the Mann-Whitney U test for non-parametric or ordinal data. Categorical data was compared using the Chi-Square test or Fisher’s Exact test, as appropriate. The study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.¹⁸ To reduce potential imbalance of baseline characteristics between patients with and without desmopressin we used propensity score matching. The propensity score was defined as the probability of a patient receiving desmopressin given their age, sex, NIHSS score at baseline, and ICH score at baseline, as estimated using a multivariable logistic regression model. For each patient who received desmopressin, four patients who did not were matched based on the logit of the propensity score (± 0.2 standard deviations of the propensity score). All data collected from participants was entered by each investigator into a secured data REDCap© repository ((Version 6.18.1, 2019; Vanderbilt University, Nashville, TN).

Overall, 1408 patients were evaluated for inclusion during the study period, of which 1084 were excluded. The most common reasons for exclusion were no follow up head CT within 24 hours (±6 hours) of initial CT (n=271), isolated traumatic brain injury (n=284), concurrent ischemic stroke (n=202), neurosurgical interventions within 12 hours of admission (n=109), and missing information (n=44). A total of 324 patients were included, of which 45 received desmopressin. After propensity score matching, there were 35 patients in the desmopressin group and 140 in the control group.

Baseline demographics were similar between groups, with some notable exceptions (Table 1). There were more black patients in the desmopressin group (11.4% desmopressin group vs. 1.4% control group, p=0.02) and more white patients in the control group (68.6% vs. 95.7%). Comorbid conditions were similar between groups apart from end stage renal disease (ESRD) which was more common in the desmopressin group (20% vs. 1.4%) and cancer (28.6% vs. 12.1%). The most common type of ICH was intraparenchymal hemorrhage (100% of both groups). Baseline hematoma volume (27mL vs. 2.1 mL) was significantly higher in the desmopressin group. Patients in the desmopressin group had higher baseline serum creatinine (1.2 vs. 1 mg/dL). Anticoagulant use was similar between groups and most patients were on aspirin in both groups (100% vs. 94.3%).

There were no differences between groups in terms of use of concomitant hemostatic agents (Table 2). The most common hemostatic agent was four factor prothrombin complex concentrate in both groups (22.9% desmopressin group vs. 14.3% control group). The desmopressin group received a median dose of 26 mcg of desmopressin (median dose of 0.3 mcg/kg, interquartile range [IQR] 0.3 – 0.4). Median time to desmopressin administration was 163 (IQR 111 – 356) minutes. Blood product use was similar between groups, except for more packed red blood cells (PRBCs) in the desmopressin group (11.1% vs. 1%, p<0.01). More patients in the desmopressin group had neurosurgical interventions including burr hole placement and craniotomy.

The primary endpoint of good or excellent hemostatic efficacy was similar between groups (74.3% desmopressin group vs. 85% control group, -10.7% [-28.1% to 6.7%]; Table 3). There was no difference in the change in hematoma volume, maximum thickness, serum sodium nadir, or adverse events between groups. Patients in the desmopressin group had higher median NIHSS scores at discharge (11 vs. 2.5, p=0.62), though this was not statistically significant. There was also no difference in discharge disposition or in-hospital or 30-day mortality.

Our multicenter, retrospective propensity-matched study did not demonstrate improved rates of good or excellent hemostatic efficacy in patients receiving early desmopressin for the treatment of ICH. Additionally, desmopressin was not associated with an observed increase in adverse events. Desmopressin was administered to patients with more severe disease at baseline, as evidenced by higher NIHSS, as well as significantly larger hematoma volumes at baseline. This suggests that with more severe disease, providers may be more likely to intervene with desmopressin.

Limited evidence exists to guide therapy in antiplatelet-related ICH. A small, prospective study of 14 patients demonstrated that desmopressin improved platelet activity in ICH, but did not assess clinical outcomes.⁷ A single center retrospective study of 124 patients found that desmopressin may decrease likelihood of hematoma expansion in the first 24 hours of ICH.¹⁰ In contrast, the largest study to date was a multicenter retrospective study including 209 patients that found no difference in the incidence of hematoma expansion in patients who received desmopressin compared to those who did not.⁶ A smaller study of 71 patients with antiplatelet-related ICH also did not find that desmopressin impacted hematoma expansion. A retrospective cohort of 140 patients presenting with antiplatelet-related ICH showed no difference in hematoma expansion when comparing desmopressin 0.4 mcg/kg plus two units of platelets to a control group.¹⁹ Only one randomized trial has been conducted including 54 patients (n=27 in both desmopressin 20 mcg and placebo groups).¹⁴ However, the goal of this study was feasibility in terms of the number of subjects randomized and did not detect meaningful differences in outcomes. While previous observational data is conflicting, our study demonstrates that in a geographically diverse cohort in 11 centers, desmopressin did not appear to impact hemostatic efficacy or functional outcomes.

Desmopressin is an antidiuretic hormone analog that causes water reabsorption in the kidneys, which may result in hypervolemic hyponatremia.²⁰ Administering desmopressin in patients with ICH who frequently require medications such as hypertonic saline (HTS) to mitigate intracranial pressure and cerebral edema could lead to AEs.²¹ A retrospective study including 50 patients with antiplatelet-related ICH evaluated the effect of desmopressin on reaching a sodium goal of 145-155 mEq/L in patients needing hypertonic saline for cerebral edema.²² Desmopressin did not impede reaching this goal. However, when the goal was higher (e.g., 150-155 mEq/L), patients were less frequently within goal sodium targets.²² We did not find a difference in sodium serum concentration nadir between patients who did or did not receive desmopressin, but because there is lack of evidence supporting improved hemostatic efficacy, desmopressin use should remain limited especially in patients who require higher sodium goals.

There is limited data exploring the appropriate dose of desmopressin in the setting of antiplatelet-related bleeding. The median dose used in our cohort was 26.2 mcg and the actual body weight-based dose was 0.3 mcg/kg (IQR 0.3 – 0.4). This is lower than recommended in clinical practice guidelines, which recommends 0.4 mcg/kg.¹ The optimal dose in antiplatelet-related ICH is unknown and should be further explored.

This study has several limitations, including its retrospective design and reliance on documentation. Less patients received desmopressin than anticipated, with the desmopressin group comprising only 7.2% of patients in our study. This is surprising given that the Neurocritical Care Society/Society of Critical Care Medicine suggest the use of desmopressin in this cohort.¹ Also, given the retrospective nature of our study, we had no way to assess when patients took their last dose of antiplatelet agent, and aspirin comprised the majority of our antiplatelet use. Few patients received dual antiplatelet therapy; this cohort warrants further exploration. We also did not collect data on blood pressure or ICP management, which may influence outcomes in ICH.²³ Additionally, we only included spontaneous ICH and results should not be extrapolated to traumatic brain injury. Finally, there were several notable differences in baseline demographics, including more severe disease in the desmopressin group, as evident by larger hematoma volumes and maximum thickness.

In this retrospective, multicenter study at 11 EDs around the US, desmopressin did not impact hemostatic efficacy, functional outcomes, or adverse effects in patients with antiplatelet-related ICH. Though randomized, controlled trials are needed to further explore the role of desmopressin in the management of antiplatelet-related ICH, this study supports the decision to withhold desmopressin in this setting.

Relevant disclosures:

CSB has received grant funding from Alexion/Astra Zeneca.

BWG has received consultant and speaker fees from Haemonetics.

GWS has received advisory board fee from Hema Biologics.

MAR, GTH CNT, LR, TF, NGP, MA, BPG, UK, RYN, ED, AKS, SS, PV, BAF, DA, AM, SD, TF, LG, GTH, JL, KM, JSN, NGP, LR, PS, CNT, JAW have no conflicts of interest to disclose.

Acknowledgement:

Gabrielle Morrow PharmD, University of Iowa

Lauren Gravert, PharmD student, University of Iowa

Funding: This study was partially funded by a grant from Mayo Midwest Pharmacy Research Committee.

Author roles: MAR: conceptualization, design, data collection, data analysis, interpretation, manuscript writing and editing; CB, GWS, BWG, BAF: conceptualization, design, data collection, interpretation, manuscript editing; DA, AM: 3D-Slicer trainers, hematoma volume reading experts and organization, manuscript editing; MA, BPG, UK, RYN, ED, AKS, SS, PV: hematoma volume reading, data collection, manuscript editing; SD, TF, LG, GTH, JL, KM, JSN, NGP, LR, PS, CNT, JAW: data collection, manuscript editing. All authors approved the final approval of the manuscript and agree to be accountable for all aspects of the work.

Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocritical Care. 2016;24(1):6-46. doi:10.1007/s12028-015-0222-x
Rost NS, Smith EE, Chang Y, et al. Prediction of Functional Outcome in Patients With Primary Intracerebral Hemorrhage. Stroke. 2008;39(8):2304-2309. doi:10.1161/STROKEAHA.107.512202
Dowlatshahi D, Demchuk AM, Flaherty ML, Ali M, Lyden PL, Smith EE. Defining hematoma expansion in intracerebral hemorrhage. Neurology. 2011;76(14):1238-1244. doi:10.1212/WNL.0b013e3182143317
Al-Shahi Salman R, Frantzias J, Lee RJ, et al. Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data. The Lancet Neurology. 2018;17(10):885-894. doi:10.1016/S1474-4422(18)30253-9
Roquer J, Vivanco Hidalgo RM, Ois A, et al. Antithrombotic pretreatment increases very-early mortality in primary intracerebral hemorrhage. Neurology. 2017;88(9):885-891. doi:10.1212/WNL.0000000000003659
Summers A, Singh J, Lai M, et al. A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage. Thromb Res. 2023;222:96-101. doi:10.1016/j.thromres.2022.12.016
Naidech AM, Maas MB, Levasseur-Franklin KE, et al. Desmopressin improves platelet activity in acute intracerebral hemorrhage. Stroke; a journal of cerebral circulation. 2014;45(8):2451-2453. doi:10.1161/STROKEAHA.114.006061
Spahn DR, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Critical care (London, England). 2019;23(1):98. doi:10.1186/s13054-019-2347-3
Colucci G, Stutz M, Rochat S, et al. The effect of desmopressin on platelet function: A selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects. Blood. 2014;123(12):1905-1916. doi:10.1182/blood-2013-04-497123
Feldman EA, Meola G, Zyck S, et al. Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients with Antiplatelet-Associated Intracranial Hemorrhage∗. Critical Care Medicine. 2019;47(12):1759-1765. doi:10.1097/CCM.0000000000004021
Schmidt KJ, Sager B, Zachariah J, Raad BF, James EG, Fletcher JJ. Cohort analysis of desmopressin effect on hematoma expansion in patients with spontaneous intracerebral hemorrhage and documented pre-ictus antiplatelet use. Journal of Clinical Neuroscience. 2019;66:33-37. doi:10.1016/j.jocn.2019.05.032
McManus J, Ferreira J, Jones GM, et al. Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy. J Neurol Sci. 2022;434:120142. doi:10.1016/j.jns.2022.120142
Glass NE, Riccardi J, Horng H, Kacprzynski G, Sifri Z. Platelet dysfunction in patients with traumatic intracranial hemorrhage: Do desmopressin and platelet therapy help or harm? Am J Surg. 2022;223(1):131-136. doi:10.1016/j.amjsurg.2021.07.050
Desborough MJR, Al-Shahi Salman R, Stanworth SJ, et al. Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial. Lancet Neurol. 2023;22(7):557-567. doi:10.1016/S1474-4422(23)00157-6
Khorsand N, Majeed A, Sarode R, Beyer-Westendorf J, Schulman S, Meijer K. Assessment of effectiveness of major bleeding management: proposed definitions for effective hemostasis: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2016;14(1):211-214. doi:10.1111/jth.13148
Sarode R, Milling TJ, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: A randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234-1243. doi:10.1161/CIRCULATIONAHA.113.002283
3D Slicer image computing platform. 3D Slicer. Accessed November 3, 2023. https://slicer.org/
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Journal of clinical epidemiology. 2008;61(4):344-349. doi:10.1016/J.JCLINEPI.2007.11.008
Mengel A, Stefanou MI, Hadaschik KA, et al. Early Administration of Desmopressin and Platelet Transfusion for Reducing Hematoma Expansion in Patients With Acute Antiplatelet Therapy Associated Intracerebral Hemorrhage. Crit Care Med. 2020;48(7):1009-1017. doi:10.1097/CCM.0000000000004348
Stoof SCM, Cnossen MH, de Maat MPM, Leebeek FWG, Kruip MJHA. Side effects of desmopressin in patients with bleeding disorders. Haemophilia. 2016;22(1):39-45. doi:10.1111/hae.12732
Cook AM, Morgan Jones G, Hawryluk GWJ, et al. Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocrit Care. 2020;32(3):647-666. doi:10.1007/s12028-020-00959-7
Bowers E, Shaw E, Bromberg W, Johnson A. Desmopressin Administration and Impact on Hypertonic Saline Effectiveness in Intracranial Hemorrhage. Neurocrit Care. 2022;36(1):164-170. doi:10.1007/s12028-021-01277-2
Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. New England Journal of Medicine. 2016;375(11):1033-1043. doi:10.1056/NEJMoa1603460

Table 1. Baseline Demographics

Characteristic	Desmopressin Group (N=35)	Control Group (n=140)
Age, years, median (interquartile range, IQR)	73 (66 – 79)	77 (67 – 83)
Sex, male, n (%)	21 (60.0)	83 (59.3)
Race, n (%) Black White Other	4 (11.4) 24 (68.6) 2 (5.7)	2 (1.4) 134 (95.7) 1 (0.7)
Hispanic ethnicity, n (%)	4 (11.4)	6 (4.3)
Body mass index, kg/m², median (IQR)	27.3 (23.3 – 30.8)	26.6 (23.6 – 32.0)
Weight, kg, median (IQR)	79.1 (60.2 – 88.5)	80.3 (66.0 – 95.3)
Comorbid conditions, n (%) Atrial fibrillation Cancer Coronary artery disease Diabetes End stage renal disease Hypertension Venous thromboembolism	10 (28.6) 10 (28.6) 12 (34.3) 9 (25.7) 7 (20.0) 29 (82.9) 3 (8.6)	32 (22.9) 17 (12.1) 41 (29.3) 38 (27.1) 2 (1.4) 116 (82.9) 4 (2.9)
Social history, n (%) Tobacco Alcohol	5 (14.3) 6 (17.1)	15 (10.7) 42 (30.0)
Type of ICH, n (%) Epidural hematoma Intraparenchymal hemorrhage (IPH) Subdural hematoma Subarachnoid hemorrhage (SDH)	0 (0) 35 (100.0) 1 (2.6) 3 (8.6)	1 (0.7) 140 (100.0) 0 (0.0) 2 (1.4)
Glasgow Coma Scale, median (IQR)	13 (9 – 15)	14 (8 – 15)
National Institute of Health Stroke Scale, median (IQR)	11 (8 – 18)	6 (3 – 17)
ICH score, median (IQR)	2 (1 – 3)	2 (1 – 2)
Baseline ICH measurements, median (IQR) IPH hematoma volume, mL SDH maximum thickness, mm (n=4)	27.6 (4.6 – 56.7) 52.3 (26.5 – 71.5)	2.1 (0.5 – 6.1) --
Baseline vital signs & laboratory parameters, median (IQR) Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg International normalized ratio (INR) Hemoglobin, mg/dL Platelets, ×10⁹/L Sodium, mg/dL Creatinine, mg/dL Blood urea nitrogen, mg/dL	169.5 (131– 184) 88 (75 – 101) 1.1 (1 – 1.2) 13.6 (11.9 – 14.4) 190 (159 – 245) 140 (137 – 142) 1.2 (0.8 – 1.6) 17 (14 – 25)	154 (134 – 169) 82 (72 – 95) 1.1 (1 – 1.2) 13.4 (12.1 – 14.9) 206 (166 – 254) 139 (135 – 141) 1 (0.8 – 1.2) 18 (14 – 23)
Anticoagulants, n (%) Apixaban Dabigatran Rivaroxaban Warfarin	2 (5.7) 0 (0) 1 (2.9) 5 (14.3)	12 (8.6) 0 (0) 3 (2.1) 19 (13.6)
Antiplatelet agents, n (%) Aspirin Clopidogrel Other	35 (100.0) 5 (14.3) 0 (0)	132 (94.3) 26 (18.6) 4 (2.9)

Table 2. Hemostatic and Surgical Management

Hemostatic and Surgical Management

Desmopressin Group (N=35)

Control Group (n=140)

Hemostatic agents, n (%)

Andexanet alfa

Factor eight inhibitor bypassing agent (FEIBA)

Four-factor prothrombin complex concentrate

Protamine

Tranexamic acid

Vitamin K

0 (0)

8 (22.9)

2 (5.7)

0 (0)

4 (11.4)

2 (1.4)

0 (0)

20 (14.3)

2 (1.4)

0 (0)

16 (11.4)

Desmopressin, median (IQR)

Dose, mcg

Dose, mcg/kg

Time to desmopressin, minutes

26 (20 – 32)

0.3 (0.3 – 0.4)

163 (111 – 356)

Blood products, n (%)

Cryoprecipitate

Fresh frozen plasma

Platelets

Packed red blood cells

2 (5.7)

0 (0)

7 (20.0)

4 (11.4)

1 (0.7)

4 (2.9)

13 (9.3)

1 (0.7)

Surgical interventions, n (%)

Burr hole

Clip or coil of aneurysm

Craniectomy

Craniotomy

2 (5.7)

0 (0)

1 (2.9)

2 (5.7)

0 (0)

2 (1.4)

3 (2.1)

Table 3. Outcomes

Outcome

Desmopressin Group (N=35)

Control Group (n=140)

Difference (95% CI)

Hemostatic efficacy, n (%)

Good or excellent

Poor

26 (74.3)

9 (25.7)

119 (85.0)

21 (15.0)

-10.7% (-28.1% to 6.7%)

10.7% (-6.7% to 28.1%)

Repeat ICH measurements, median (IQR)

Hematoma volume, mL

Change, hematoma volume, mL

% Change, hematoma volume

Hematoma expansion

<20%

≥20%

Maximum thickness, mm (N=4)

Change, maximum thickness, mm (N=4)

32.1 (7.6 – 59.6)

0.9 (0 – 9.6)

4.9 (-0.5 – 37.3)

24 (68.6)

11 (31.4)

54.5 (27 – 71)

0.5 (-2.3 – 2.3)

2.3 (0.6 – 8.4)

0.1 (0.0 – 0.6)

7.9 (0.8 – 17.0)

110 (79.1)

29 (20.9)

24.9 (11.7 to 32.5)

0.55 (-0.01 to 2.59)

-0.1 (-5.0 to 5.9)

-10.5% (-29.2% to 8.0%)

10.5% (-8.0% to 29.2%)

Serum sodium nadir, median (IQR)

138 (135 – 140)

1 (-1 to 2)

Adverse events within 7 days, n (%)

Ischemic stroke

Myocardial infarction

Venous thromboembolism

0 (0)

3 (2.1)

1 (0.7)

-2.1% (-6.3% to 2.0%)

-0.7% (-2.8% to 1.4%)

mRS, discharge, median (IQR; n=36)

5 (5 – 6)

5 (3 – 6)

1 (0 to 2)

NIHSS, discharge, median (IQR; n=38)

11 (2 – 11)

2.5 (1 – 10.5)

1 (-6 to 10)

Discharge disposition, n (%)

Home

Hospice

Long-term care facility/nursing home

7 (20.6)

1 (2.9)

13 (38.2)

19 (13.7)

10 (7.2)

73 (52.5)

6.9% (-9.7% to 23.5%)

-4.3% (-13.2% to 4.7%)

-14.3% (-34.4% to 5.9%)

Mortality, n (%)

Hospital

30-day

13 (37.1)

14 (40.0)

38 (27.3)

48 (35.6)

9.8% (-9.6% to 29.2%)

4.4% (-15.5% to 24.4%)

Download PDF

Reviewers agreed at journal
09 Aug, 2024
Reviewers invited by journal
07 Aug, 2024
Editor invited by journal
26 Jun, 2024
Editor assigned by journal
26 Jun, 2024
First submitted to journal
25 Jun, 2024

You are reading this latest preprint version

Impact of Desmopressin ON HemaToma EXPANsion in Patients Presenting to the Emergency Department on Antiplatelet Therapy: DON'T EXPAND Study

Status:

Version 1

Abstract

Introduction

Methods

Results

Discussion

Conclusion

Declarations

References

Tables

Status:

Version 1