Case Vignette
DP is a 70-year-old male with a past medical history significant for peripheral vascular disease (PVD) on clopidogrel who presents with acute intracranial hemorrhage. The team is discussing antithrombotic reversal treatment options.
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ACEP Now May 03When?
It is reasonable to consider the use of desmopressin (DDAVP) for patients with life-threatening bleeding with platelet dysfunction or in the setting of anti-platelet therapy.
Why?
DDAVP causes release of endogenous coagulation factors such as factor VIII, von Willebrand factor (vWF), and tissue plasminogen activator (tPA) which increases plasma factor levels, enhances platelet adhesion, and reduces bleeding time. vWF is responsible for platelet adhesion to collagen and may also bind platelets through their glycoprotein IIb/IIIa receptors. Increased vWF may help compensate for the platelet dysfunction caused by antiplatelet agents.
How?
- Dose: 0.3-0.4 mcg/kg IV infused over 30 minutes
- Onset: within 30 minutes
- Peak effect: 1.5-2 hours
- Duration: ~6-14 hours
- Adverse effects: tachycardia, hypotension, hyponatremia/seizures, hypervolemia, facial flushing, peripheral edema, decreased urine output
- Warning/Precautions: thrombotic events, coronary artery insufficiency, fluid retention, severe hyponatremia, allergic reactions or anaphylaxis
Overview of Evidence
| Author, year | Design/ sample size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Shahzad F, et al; 2024. | Meta-analysis including all randomized controlled trials, cohort studies, case-control studies and case series of patients with intracranial hemorrhage (ICH)
N = 598 |
DDAVP (n = 301)
Vs Control (n = 297) |
Risk of hematoma expansion reduced (18.4% vs 25%; p=0.31)
No difference in thrombotic events |
| Feldman E, et al; 2019. | Retrospective chart review
N = 124 |
Adult patients with a diagnosis of ICH and on antiplatelet therapy
DDAVP (n = 55) Vs No DDAVP (n = 69) |
In-hospital mortality was similar between groups (27.3% vs 21.7%; p=0.475)
Changes in ICH volume on repeat CT were smaller in the DDAVP group ICH expansion less likely during the first treatment day in the DDAVP group Odds of stable or decreased ICH volume on repeat CT scan were greater in the DDAVP group (72.7% vs 40.6%; p<0.001) |
| Desborough M, et al; 2017. | Systematic Review and meta-analysis of randomized controlled trials
N = 596 |
Platelet dysfunction due to antiplatelet agent in 6 trials and cardiopulmonary bypass in 4 trials – all treated with DDAVP | Patients treated with desmopressin: -were transfused with fewer red cells ( -0.65 units; 95% CI –1.16 to –0.13) -lost less blood ( -253.93 mL; 95% CI, -408.01 to –99.85 mL) -had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18-0.84) |
| Barletta J, et al; 2016. | Retrospective study
N = 130 |
Patients who were taking an antiplatelet medication and received intravenous DDAVP 0.3 mcg/kg for traumatic brain injury or hemorrhagic stroke | Incidence of DDAVP-associated thrombosis was 1.5%
Hematoma expansion occurred in 19% of patients, and of those, 44% were symptomatic and 16% required an operation Good neurologic function was seen in 79% of patients at discharge and average GCS was 13 Hospital mortality was 8.5% |
| Kapapa T, et al; 2014. | Prospective, interventional study
N = 13 |
4 patients received a single dose of aspirin, 6 patients received multiple doses of aspirin, and 3 patients had not received any aspirin (control group) | -Platelet function was found to be impaired in patients who took a single dose and multiple doses of aspirin at T1 (prior to DDAVP initiation)
-Platelet function had returned to normal in patients who took a single dose and multiple doses of aspirin at T2 (a half an hour after DDAVP administration) -Platelet function was again impaired in patients who took a single dose and multiple doses of aspirin at T3, though values were worse in patients who took multiple doses (three hours after DDAVP administration) -DDAVP concluded to safely stabilize the platelet function in patients with intracranial hemorrhage taking aspirin |
| Naidech A, et al; 2014. | Prospective study
N = 14 |
Patients had either known aspirin use or reduced platelet activity and received desmopressin 0.4 mcg/kg IV for 30 minutes | Platelet function analyzer-epinephrine decreased from 192 to 124 seconds (p=0.01), which is consistent with a resolution of an aspirin effect.
vWF antigen increased from 242 to 289 activity (p=0.004) indicating that desmopressin administration was associated with increased vWF levels Median change in hematoma volume was –0.5 (-1.4 to 8.4) mL One patient had hypotension (7%) and another had a new fever within 6 hours of infusion start |
Dr. May is an emergency medicine pharmacy specialist at Carolinas Medical Center in Charlotte, NC.
Dr. Gibbs is the chair of the department of emergency medicine at Carolinas Medical Center in Charlotte, NC.
References
- Micromedex® 2.0 (Healthcare Series), (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA.
- Frontera J, et al. “Guideline for Reversal of Antithrombotics in Intracranial Hemorhage.” Neurocrit Care. 2016; 24:6-46.
- Desborough M, et al. “Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial.” The Lancet: Neurology. 2023; 22(7): 557-567.
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