Abstract Number: LPB0068
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Management of Bleeding and Trauma
Background: Desmopressin (DDAVP) is a proven therapy for bleeding disorders, however, the therapeutic efficacy of different formulations has yet to be systematically analyzed.
Aims: This study investigates whether subcutaneous (SC) DDAVP provides equivalent hemostatic efficacy to intravenous (IV) desmopressin, particularly in patients with mild to moderate bleeding tendencies from hemophilia A or von Willebrand disease (vWd).
Methods: We searched PubMed, EMBASE, MEDLINE, Cochrane, and CINAHL databases for observational studies and randomized controlled trials, which compared the hemostatic efficacy of parenteral formulations of desmopressin in healthy patients, or those living with bleeding disorders. The references of included studies were also analyzed for potential inclusion in our study. To systematically analyze all available data, no restrictions were placed on the publication period of this review. Two reviewers independently performed screening and data extraction. Extracted data included laboratory measurements of hemostatic efficacy such as Factor VIII (FVIII) levels, as well as levels of von Willebrand factor antigen (vWF:Ag) and vWF activity.
Results: The search strategy yielded a total of 5519 studies. Twelve studies met the inclusion criteria and were included in the review. All four studies conducted in healthy subjects (Table 1) and seven out of eight studies conducted in patients with bleeding disorders found no difference in laboratory markers of hemostatic efficacy (Table 2). No studies utilized clinical outcomes to measure hemostatic efficacy. The average number of participants per study was 39.
| Study | Number of Participants (n) | Patient Population | Main Outcomes of Interest | Main Conclusions |
|---|---|---|---|---|
| Kohler, 1986 | 10 | Healthy patients | FVIII:C, FXII, HMW-kininogen levels, ristocetin cofactor (vWF:Ag); also measured half-life, FVIII:Ag | SC formulations were found to have efficacy more similar to IV forms than intranasal compounds. |
| Kohler, 1988 | 10 | Healthy patients | FVIII:Ag, t-PA, leukocyte count, bioavailability | There was no significant difference between SC and IV formulations in FVIII:Ag, t-PA antigen, or leukocyte counts. No significant difference in response rate, half-life or area under the curve (AUC) for bioavailability in IV and SC forms. |
| MacGregor, 1988 | 6 | Healthy patients | t-PA, t-PA:Ag, FVIII, FVIII:Ag, vWF:Ag, PAI | SC formulations had almost double the time to maximal increase in main outcomes as compared to IV. Fibrinolytic response to SC was proportionate to the hemostatic response from the same dosage of IV formulation. |
| Törnebohm, 1992 | 6 | Healthy patients | t-PA |
SC took longer to achieve half-maximal concentration; no significant difference in t-PA response in AUC between SC and IV formulations. Elimination was similar, regardless of formulation. |
| FVIII = factor VIII; FVIII:Ag = factor VIII antigen; FVIII:C = factor VIII activity; FXII = factor XII; HMW-kininogen = high molecular weight-kininogen; PAI = plasminogen activator inhibitor; t-PA = tissue plasminogen activator; t-PA:Ag = tissue plasminogen activator antigen; vWF:Ag = von Willebrand factor antigen | ||||
Studies investigating hemostatic efficacy in healthy patients
| Study | Number of Participants (n) | Patient Population | Main Outcomes of Interest | Main Conclusions |
|---|---|---|---|---|
| Kohler, 1984 | 53 | Mild to moderate hemophilia A and mild vWd | FVIII:C, FVIIIR:Ag, FVIII:Rcof | SC administration offered a consistent and reliable hemostatic response in place of IV administration. |
| De Sio, 1985 | 26 | Mild to moderate hemophilia A | FVIII:C | The response to DDAVP after 60 minutes did not statistically differ between formulations. |
| Ghirardini, 1987 | 59 | Mild hemophilia and Type 1 vWd | FVIII:C | There were no statistically significant differences between IV or either SC formulations (concentrated vs. diluted). |
| Mannucci, 1987 | 14 | Mild to moderate hemophilia A | FVIII:C; measured peak DDAVP, time to peak levels, time curve, and half-life | No significant difference in mean FVIII:C levels between IV and SC. No differences in half-life or AUC values between IV and SC formulations. |
| Grana, 1990 | 11 | Hemophilia A, vWd, or a primary platelet aggregation disorder | FVIII:Ag, FVIII:C | No significant difference in the mean increase in FVIII:Ag between IV and SC formulations. Hemostatic response and correction of bleeding time was comparable between IV and SC forms. |
| Jensen, 1997 | 22 | Mild hemophilia A | FVIII:C, vWF:Ag, APTT | No significant difference in response of FVIII:C between routes of administration. |
| Knofler, 2012 | 80 | Hemophilia A or carriers | FVIII:C | The magnitude of FVIII:C response between IV and SC forms was relatively equal (p-value not reported). |
| Loomans, 2018 | 169 | Moderate hemophilia A | FVIII:C | There was no significant difference between formulations in vWF:Ag levels, IV had a significantly higher peak FVIII:C (p<0.001). |
| APTT = activated partial thromboplastin time; FVIII:Ag = factor VIII antigen; FVIII:C = factor VIII activity; FVIII:Rcof = factor VIII ristocetin cofactor; FVIIIR:Ag = factor VIII related antigen; vWF:Ag = von Willebrand factor antigen | ||||
Studies investigating hemostatic efficacy in patients with hemophilia A or vWd
Conclusions: This is the first systematic review to date to evaluate the hemostatic efficacy of parenteral DDAVP formulations. Our study shows that IV and SC administration of DDAVP appears to result in a near equivalent rise of laboratory hemostatic markers; however, these findings are limited by the overall under-sampling of primary studies, necessitating larger and more recent randomized controlled trials to provide further clarification.
To cite this abstract in AMA style:
McKinlay S, Sreeraman S, Motalo O, Li A, Crowther M. Efficacy of Parenteral Formulations of Desmopressin in the Treatment of Bleeding Disorders: A Systematic Review [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/efficacy-of-parenteral-formulations-of-desmopressin-in-the-treatment-of-bleeding-disorders-a-systematic-review/. Accessed December 10, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/efficacy-of-parenteral-formulations-of-desmopressin-in-the-treatment-of-bleeding-disorders-a-systematic-review/