Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders [see comments]

Desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of factor VIII coagulant activity (FVIII) and von Willebrand factor and shorten the prolonged bleeding time, DDAVP is established as a nontransfusional form of treatment for mild and moderate hemophilia and von Willebrand disease. Recently, DDAVP has also been purported to be useful for shortening the prolonged skin bleeding times that occur with uremia, cirrhosis, and platelet dysfunctions of various etiologies. Finally, there is evidence from controlled clinical trials that DDAVP can reduce blood loss and transfusion requirements for hemostatically normal individuals undergoing spinal fusion surgery and for patients undergoing cardiopulmonary bypass surgery. The purpose of this report is to review the therapeutic applications of DDAVP in congenital and acquired bleeding disorders and to discuss areas in which further basic and clinical research is needed.     

Proteolysis of von Willebrand factor in therapeutic plasma concentrates

Therapeutic plasma concentrates containing vo Willebrand factor (vWF) lack the largest, most hemostatically active multimers. To evaluate whether this abnormality results from proteolysis during manufacturing, we have analyzed the subunit structure of vWF in several commercial products and found a marked reduction in the relative content of intact 225-kD subunit, paralleled by an increase in the proteolytic fragments normally present in plasma, particularly that of 176 kD. There was no heightened vWF fragmentation in blood-bank cryoprecipitate prepared from platelet-poor, single-donor plasma; in contrast, there was a marked degree of fragmentation in cryoprecipitate prepared from pooled plasmapheresis plasma representing the starting fraction for the production of commercial concentrates. In cryoprecipitate prepared experimentally from plasma containing varying numbers of platelets, the degradation of vWF was proportional to the platelet count, but was greatly diminished by adding protease inhibitors to the plasma. On the basis of these findings, we postulate that the loss of the largest vWF multimers in commercial products results from the use of poorly centrifuged plasmapheresis plasma containing an excessive number of residual platelets and leukocytes. These cells, lysing when plasma is frozen and thawed for the preparation of cryoprecipitate, may liberate proteolytic enzymes that cleave the vWF subunit and contribute to the degradation of the largest multimers. Our results should help devise new approaches for the preparation of more effective concentrates for the treatment of von Willebrand disease.     

Assessment of pain: can caregivers or relatives rate pain in nursing home residents?

Aim. To compare pain reports of nursing home residents to ratings by proxies. Background. It is not easy to assess pain in cognitively impaired residents. For residents who are unable to report pain intensity themselves, proxies (i.e. relatives or caregivers) might serve as sources of information. The utility of these proxies in assessing residents’ pain is not clear however. Design. A multicenter cross‐sectional study. Methods. Pain intensity was rated on a Numeric Rating Scale; proxies were asked how certain they were about their observations. Agreements on ratings were computed by means of intra class correlation (ICC) coefficients for continuous variables and multiple linear regression analyses were performed with the level of pain intensity by proxies as the dependent variable. Results. The sample consisted of 174 residents (median age 82 years), of whom 124 were cognitively impaired and 50 intact, and 293 proxies: 171 caregivers and 122 relatives. All three parties reported median pain intensity during the preceding week as 6·0. Data were consistent with low‐to‐moderate correlation coefficients between residents and caregivers (ICC = ?0·12 to 0·25), residents and relatives (ICC = ?0·51 to 0·48) and caregivers and relatives (ICC = 0·03 to 0·31). Residents themselves judged pain intensity at rest significantly higher than did proxies (p = 0·05). Caregivers scored significantly higher ratings for residents on analgesics (p = 0·001) and significantly lower pain ratings if they were more satisfied with the prescribed analgesics (p = 0·01). Conclusions. Proxy report of relatives and caregivers on presence and intensity of pain is unreliable, especially for cognitively impaired persons. The use of a standardised pain observation scale could be helpful. Relevance to clinical practice. Pain management in nursing home residents could be improved by educating caregivers about assessment and treatment of chronic pain. Relatives should be informed about chronic pain and learn how to alleviate pain through non‐pharmacological interventions.