Unclassified bleeding disorders: outcome of haemostatic challenges following tranexamic acid and/or desmopressin.

INTRODUCTION: In a minority of patients with a significant bleeding history no cause is found despite extensive testing and we diagnose such cases as unclassified bleeding disorders (UBD). UBDs may have diverse underlying causes and currently no standard management strategy exists in the event of a haemorrhage or to cover surgery. AIM: To document the clinical characteristics and response to treatment of UBDs. METHODS: We performed a retrospective chart review of all patients with UBDs who had an invasive procedure at our centre between 1998 and 2014. RESULTS: The commonest symptoms were menorrhagia (89%) and bleeding at the time of surgery (88%) or dental extraction (85%). A total of 33 patients underwent 78 minor and major haemostatic challenges. Haemostatic cover was provided in 28 procedures with tranexamic acid alone, two with desmopressin and 45 with both agents in combination. A successful haemostatic outcome was observed in 70/78 (90%) cases. No patient required additional surgical intervention to achieve haemostasis, but one patient required a platelet transfusion to control postoperative bleeding. CONCLUSIONS: This is the first study to report on the investigation and treatment of UBD. Future studies are needed to further our understanding of the bleeding phenotype and identify any underlying causes.

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

OBJECTIVE: To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN: Controlled comparative study. SETTING: London teaching hospital. PATIENTS: 33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES: Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS: In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS: Important haemodynamic disturbances were identified during routine apparently uneventful transurethral prostatectomy but not during control procedures. These responses may be related to the rapid central cooling observed during transurethral prostatectomy and require further study.

Assessment of thrombin generation measured before and after cardiopulmonary bypass surgery and its association with postoperative bleeding.

BACKGROUND: Bleeding after cardiopulmonary bypass (CPB) is a major cause of morbidity and mortality and consumes large amounts of blood. Identifying patients at increased risk of bleeding secondary to hemostatic impairment may improve clinical outcomes by allowing early intervention. METHODS: This present study recruited 77 patients undergoing CPB and measured coagulation screens, coagulation factors, TEG(®), Rotem(®) and thrombin generation (TG) before surgery and 30 min after heparin reversal. The tests were analyzed to investigate whether they identified patients at increased risk of excess bleeding (defined as > 1000 mL) in the first 24 h postoperatively. RESULTS: Patients who bled > 1000 mL had a lower: platelet count (P < 0.02), factors (F)IX, X and XI (P < 0.005), endogenous thrombin potential (ETP) and an initial rate of TG (P < 0.02) and higher activated partial thromboplastin time (aPTT) (P < 0.001) than patients who bled < 1000 mL. Receiver operating characteristic (ROC) analysis was significant for post-operative TG and aPTT (P < 0.001). Furthermore, reduced pre-operative TG was associated with increased postoperative bleeding (P < 0.02). Pre- and postoperative TG were correlated (ρ = 0.7, P < 0.001). TEG(®), Rotem(®) and prothrombin time (PT) at either time point were not associated with increased bleeding. CONCLUSION: These data suggest that pre-operative defects in the propagation phase of hemostasis are exacerbated during CPB, contributing to bleeding post-CPB. TG taken both pre- and postoperatively could potentially be used to identify patients at an increased risk of bleeding post-CPB.

Measurement of global haemostasis in severe haemophilia A following factor VIII infusion.

Patients with haemophilia requires different amounts of FVIII to prevent and treat bleeds. We hypothesise that this is because FVIII has variable effects on individual patients' global haemostasis. Twelve patients with severe haemophilia A were infused with 50 IU/kg FVIII and thrombin generation in platelet rich (PRP) and platelet poor plasma (PPP) and velocity of changing clot elasticity were measured preinfusion and at nine subsequent time points over 72 h. Despite a close correlation between median FVIII and median initial rate of thrombin generation (R(2) 0.94), endogenous thrombin potential (ETP; R(2) 0.94) and peak thrombin (R(2) 0.91) in PPP, there was wide inter-patient variability at each time point. There was, however, a highly predictable intra-patient relationship between FVIII level and thrombin generation. Inter-patient variability was due to both differences in FVIII levels and the variable effect FVIII had on an individuals' thrombin generation. The utility of PRP was limited because, at low-FVIII levels, only rate of thrombin generation was measurable. At low-FVIII concentrations, the rate of thrombin generation in PPP was the most useful test whilst at higher levels ETP and peak thrombin could also be used.

Cardiovascular performance and core temperature during transurethral prostatectomy.

Hemodynamic performance and core temperature were recorded during transurethral prostatectomy in 52 patients who were stratified according to cardiac symptom score and then randomized to undergo standard (31) or isothermic (21) transurethral prostatectomy. During the standard procedure ambient temperature (21C) irrigant was used, while during isothermic prostatectomy warmed irrigant at 38C was used to prevent heat loss from the bladder, and a warming blanket and humidifying filter were used to decrease cutaneous and respiratory heat loss. Core temperature decreased by a mean of 0.8C (95% confidence interval -0.9 to -0.7) during standard transurethral prostatectomy and by 0.27C (-0.4 to -0.15) during the isothermic procedure. The standard prostatectomy group showed a significant hemodynamic response consisting of increased mean arterial pressure (p < 0.0002), increased index of systemic vascular resistance (p < 0.0001), bradycardia (p < 0.02), and decreased Doppler indexes of stroke volume (p < 0.005) and cardiac output (p < 0.001). The isothermic transurethral prostatectomy group was hemodynamically stable. These differences between the groups suggest that rapid central cooling exerted a significant effect on perioperative hemodynamic performance during transurethral prostatectomy.

Haemodynamic evidence for per-operative cardiac stress during transurethral prostatectomy. Preliminary communication.

Haemodynamic changes were measured during routine transurethral prostatectomy (TURP). The heart rate and stroke volume fell progressively over the first 30 min of surgery, resulting in a steady reduction in cardiac output. There was a significant increase in left ventricular afterload from commencement of the procedure. These findings demonstrate that haemodynamic responses, which are not detectable using conventional methods of monitoring, occur during TURP. Increased left ventricular afterload indicates increased myocardial work and oxygen demand which could result in myocardial ischaemia. This may contribute to the increased cardiovascular morbidity and mortality which have been reported to occur after TURP. The possible underlying mechanisms are discussed.