The HIT Expert Probability (HEP) Score: a novel pre‐test probability model for heparin‐induced thrombocytopenia based on broad expert opinion

Summary. Background: The diagnosis of heparin‐induced thrombocytopenia (HIT) is challenging. Over‐diagnosis and over‐treatment are common. Objectives: To develop a pre‐test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding clinical decisions regarding therapy. Patients/methods: A pre‐test model, the HIT Expert Probability (HEP) Score, was constructed based on the opinions of 26 HIT experts. Fifty patients referred to a reference laboratory for HIT testing comprised the validation cohort. Two hematology trainees scored each patient using the HEP Score and a previously published clinical scoring system (4 T’s). A panel of three independent experts adjudicated the 50 patients and rendered a diagnosis of HIT likely or unlikely. All subjects underwent HIT laboratory testing with a polyspecific HIT ELISA and serotonin release assay (SRA). Results: The HEP Score exhibited significantly greater interobserver agreement [intraclass correlation coefficient: 0.88 (95% CI 0.80–0.93) vs. 0.71 (0.54–0.83)], correlation with the results of HIT laboratory testing and concordance with the diagnosis of the expert panel (area under receiver‐operating curve: 0.91 vs. 0.74, P = 0.017) than the 4 T’s. The model was 100% sensitive and 60% specific for determining the presence of HIT as defined by the expert panel and would have allowed for a 41% reduction in the number of patients receiving a direct thrombin inhibitor (DTI). Conclusion: The HEP Score is the first pre‐test clinical scoring model for HIT based on broad expert opinion, exhibited favorable operating characteristics and may permit clinicians to confidently reduce use of alternative anticoagulants. Prospective multicenter validation is warranted.     

CARDIAC ARRHYTHMIAS DURING ANAESTHESIA FOR LAPAROSCOPY

Fifty-six patients undergoing elective laparoscopy were allocatedrandomly to two groups. Group H received alcuronium and wereventilated artificially using 0.5% halothane and nitrous oxidein oxygen. Group E breathed spontaneously a mixture of enfluraneand nitrous oxide in oxygen. Arterial pressure, heart rate,tidal volume, respiratory rate and end-tidal carbon dioxidetension (PE_CO²) were monitored. The electrocardiogram (ECG)was recorded continuously using mogni-rir tape, from beforeinduction until the patient left the insufflated carbon dioxidehad been removed from the abdomen. Spontaneous ventilation withenflurane anaesthesia is a simple and safe technique for routinelaparoscopy, providing the intra-abdominal pressure does notexceed 25 mm Hg     

ANDROSTERONE GLUCURONIDE IS A MARKER OF ADRENAL HYPERANDROGENISM IN HIRSUTE WOMEN

Androsterone glucuronide (Andros-G), a dihydrotestosterone metabolite, is present in serum at concentrations at least tenfold greater than those of androstanediol glucuronide. To investigate the significance of serum androsterone glucuronide, we developed a direct radioimmunoassay for this compound and measured its levels in normal women, women with mild or severe idiopathic hirsutism (IH), hirsute women with polycystic ovarian syndrome (PCO), and non-hirsute obese women. To determine the source of Andros-G precursors, serum levels were measured before and after selective ovarian suppression with leuprolide, combined ovarian and adrenal suppression with leuprolide and dexamethasone, and adrenal stimulation with ACTH. Androsterone glucuronide levels (nmol/l; mean +/- SD) were significantly higher (P less than 0.025) in women with mild idiopathic hirsutism (IH) (185 +/- 91), severe IH (173 +/- 97), and hirsute women with polycystic ovarian syndrome (PCO) (178 +/- 102) than in normal women (110 +/- 26). Levels in non-hirsute obese women (64 +/- 19) were lower than in normal women (P less than 0.01). Baseline levels (mean +/- SEM) in hirsute women given 20 micrograms/kg/day leuprolide for 5-9 months (171 +/- 15) were not significantly changed after leuprolide alone (153 +/- 18), and were decreased after adding dexamethasone (19 +/- 6; P less than 0.001). Andros-G levels did not increase significantly in normal women 60 min after i.v. ACTH (112 +/- 14 to 126 +/- 19), but rose in IH (170 +/- 24 to 216 +/- 26; P less than 0.001) and in PCO (179 +/- 26 to 238 +/- 31; P = 0.002). We conclude that Andros-G in women arises primarily from adrenal gland precursors and is elevated in hirsute women as a group. Its levels do not correlate with the severity of hirsutism, or the presence or absence of PCO, but reflect an increased production of adrenal androgens in both IH and PCO.     

Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis

Summary.  Background:  The effect of anticoagulant prophylaxis on the prevention of deep vein thrombosis (DVT) should include an investigation of both clinical and subclinical DVT. We conducted a systematic review to determine whether anticoagulant prophylaxis reduces the risk of asymptomatic DVT compared to no prophylaxis in at-risk hospitalized medical patients. Methods:  MEDLINE, EMBASE, and the Cochrane Library were searched through March 2007 for randomized trials of anticoagulant prophylaxis for the prevention of asymptomatic DVT, assessed by venogram or ultrasound. We assessed four outcomes: all asymptomatic DVT, asymptomatic proximal DVT, major bleeding and mortality. Random effects meta-analyses were performed and results were expressed using relative risk (RR) and 95% confidence intervals (95% CIs). Results:  Four trials including 5516 patients were eligible. Our pooled analysis demonstrated that compared to placebo, anticoagulant prophylaxis was associated with a significantly lower risk of any asymptomatic DVT (RR 0.51; 95% CI 0.39–0.67) and asymptomatic proximal DVT (RR 0.45; 95% CI 0.31–0.65). Anticoagulant prophylaxis was associated with a significantly increased risk of major bleeding compared to placebo (RR 2.00; 95% CI 1.05–3.79). There was no significant difference in the pooled estimate for all-cause mortality. Anticoagulant prophylaxis conferred an absolute risk reduction of any DVT and proximal DVT of 2.6% and 1.8%, respectively, and was associated with a 0.5% absolute risk increase in major bleeding. Conclusions:  Anticoagulant prophylaxis is effective in preventing asymptomatic DVT in at-risk hospitalized medical patients but is associated with an increased bleeding risk. The therapeutic benefits of anticoagulant prophylaxis appear to outweigh the risks of bleeding.     

Isolation,identification, and characterization of a palladium complex in the catalytic deprotection of a protected peptide

The final catalytic deprotection in the large scale synthesis of thymopentin (Arg-Lys-Asp-Val-Tyr) produced an impurity which had not previously been observed. Isolation by preparative HPLC and spectroscopic characterization led to a postulated structure of the impurity as the 1: 1 thymopentin-palladium complex. A complex corresponding to the proposed structure was independently synthesized and shown to have identical chromatographic and spectroscopic properties with the isolated material. Proton and carbon (13) NMR were used to determine the coordination sites of the peptide with palladium. The susceptibility of the complex to hydrogenation indicated a possible source for its formation.