LRP1/CD91 is up-regulated in monocytes from patients with haemophilia A: a single-centre analysis.

The low-density lipoprotein receptor-related protein 1 (LRP1) is an ubiquitously expressed endocytic receptor that, among its several functions, is involved in the catabolism of coagulation factor VIII (FVIII) and in the regulation of its plasma concentrations. Although LRP1/CD91 polymorphisms have been associated with increased FVIII levels and a consequent thrombotic risk, no data are available on LRP1/CD91 expression in patients with inherited FVIII deficiency. With the aim of elucidating this issue, 45 consecutive patients with haemophilia A (HA) (18 severe, 5 moderate and 22 mild HA) were enrolled in this cross-sectional, single-centre survey. The LRP1/CD91 mean fluorescence intensity (MFI) in monocytes from HA patients was significantly higher than that detected in 90 healthy blood donors (105 vs. 67, P < 0.001). This over-expression was independent of hepatitis C virus infection status and varied according to the severity of the haemophilia, being higher in patients with more severe FVIII deficiency. In conclusion, our study documents for the first time that LRP1/CD91 is over-expressed on monocytes from HA patients, with the intensity of expression varying according to the severity of the FVIII deficiency. Further studies are needed to assess the clinical implications of these findings.

Increased fragmentation of von Willebrand factor, due to abnormal cleavage of the subunit, parallels disease activity in recurrent hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and discloses predisposition in families. The Italian Registry of Familial and Recurrent HUS/TTP.

We investigated here the changes in von Willebrand factor (vWF) multimers in recurrent, sporadic and familial forms of hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) to see whether they are actually proteolyzed in vivo in these patients. Molecular determinants of fragments in vWF were also characterized to identify possible sites of cleavage of the subunit. Unusually large vWF multimers were found in blood of 8 of 10 patients with recurrent HUS/TTP, both in the acute phase and in remission, but never in familial and sporadic cases. Instead, all of the groups showed evidence of enhanced fragmentation of vWF multimers during the acute phase. Increased fragmentation was also shown by decrease in native 225-kD vWF subunit. In recurrent and sporadic HUS/TTP, enhanced fragmentation normalized at remission, but the abnormality persisted in familial HUS/TTP patients. The latter findings suggest that patients with familial HUS/TTP may have a congenital abnormality in vWF processing. Analysis with specific monoclonal antibodies showed the presence of the normal vWF fragments with apparent molecular mass of 189, 176, and 140 kD in all patients; however, in 6 recurrent and in 5 familial cases, novel fragments that differed in size from normal ones were found. The size of these abnormal fragments differed from one patient to another and none of them was ever found in normal plasma. These results documented, for the first time in HUS/TTP, an abnormal cleavage of the vWF subunit that might account for the increased fragmentation observed in these patients.

[Anesthesia with oral ketamine]. / Anesthésie par la kétamine orale.

Oral ketamine (7.5 mg X kg-1) was used to induce general anaesthesia in fourty seven young women undergoing voluntary abortion. Additional anaesthesia was necessary eight times because pre operative consciousness remained normal, and nine times because of important intra operative reactions. A majority (78.8%) of patients appreciated this technique of anaesthesia. Absence of narcosis (17%) and intra operative analgesia (23%) and frequency of post operative nightmares may require some modifications of the method.

PIP: Ketamine was administered to 47 women aged 14-41 years who were about to undergo induced abortions. The patients received 2.5 mg of lorazepam 2 hours before the operation and 7.5 mg/kg of ketamine diluted in orange juice or water 45 minutes before. In all cases, sleep and transfer to the operating table were accomplished in calm and semidarkness. Intravenous tubes were inserted and .02 mg/kg of atropine sulfate was administered. Patients considered still conscious were given intravenous injections of ketamine 1 mg/kg. Perioperative evaluation of the quality of anesthesia was done using a 4-level scale based on reactions to stimuli. Ketamine .5 mg/kg was administered intravenously each time significant reactions were obtained. 45 minutes after oral ketamine administration, 8 patients were still conscious and received additional anesthesia. 9 of the 39 patients asleep at the preoperative evaluation required additional anesthesia during the procedure. The immediate postoperative period was calm in all cases, even though some patients later reported having had disagreeable hallucinations. 46.8% had vomiting. The frequency of vomiting declined from 54.4% to 28.8% when pure water was substituted for orange juice as the vector for the preoperative oral ketamine. Correct responses to simple questions were obtained an average of 12.4 minutes postoperatively, but all patients had periods of somnolence lasting 4.8 hours on average. 15 had partial recollections of the surgery. 78.8% of the patients stated that the anesthesia used was excellent or good. 8.5% felt it was average, and 10.6% felt it was poor. Very few publications mention oral use of ketamine. The failure rates of 17% during the preoperative evaluation and 23% during the operation were not negligible and were probably due to the very low bioavailability of ketamine administered orally and the variability of digestive absorption of ketamine from 1 subject to another. The method appears to be appropriate for use in induced abortions, but better management is required to reduce failure rates and control side effects of vomiting and disagreeable postoperative hallucinations.