Factor IX p.A37V mutation causes severe bleeding in a patient with phenprocoumon therapy.

BACKGROUND: Bleeding is the most common complication of oral anticoagulants, due to inadequate dosing. CASE PRESENTATION: This report describes the clinical course of a patient who developed severe bleeding under therapy with phenprocoumon, despite an INR in the lower therapeutic range. Strikingly, aPTT was prolonged, while factor IX activity was significantly reduced. Acquired hemophilia was excluded, due to missing detection of inhibitors. Finally, sequencing part of the factor IX gene including nucleotide position c.110 revealed a hemizygous factor IX mutation c.110C > T p (Ala37Val). CONCLUSIONS: In rare cases, missense mutations in factor IX propeptide are associated with severe bleeding complications. The substitution of alanin at position 37 to either valin or threonin (Ala37Val or Ala37Thr) leads to hypersensitivity to vitamin k antagonists.

Genetic Polymorphisms and Perioperative Bleeding in Off-Pump Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Clopidogrel use before coronary artery bypass graft surgery may increase risk for perioperative hemorrhage. The effect of genetic polymorphisms related to clopidogrel responses on bleeding during or after off-pump coronary artery bypass graft surgery is unknown. METHODS: This prospective study included 206 coronary artery disease patients scheduled for off-pump coronary artery bypass graft surgery. Genotypes were determined using Sequenom MassARRAY system. Severe bleeding was defined by the universal definition of perioperative bleeding in cardiac surgery. RESULTS: Patients carrying the ABCB1 3435 wild-type genotype (CC) had a higher risk of severe perioperative bleeding compared with patients carrying the variant genotype (CT or TT; 33.9% vs 16.5%, P = .009). Low baseline hemoglobin level (odds ratio 0.944; 95% confidence interval, 0.917 to 0.972; P < .001), low baseline estimated glomerular filtration rate (odds ratio 0.977; 95% confidence interval, 0.956 to 0.999; P = .041), discontinuing clopidogrel 5 days or less before surgery (odds ratio 2.458; 95% confidence interval, 1.044 to 5.786; P = .039), and the ABCB1 wild-type genotype (CC; odds ratio 2.941; 95% confidence interval, 1.250 to 6.944; P = .014) were independent risk factors for severe perioperative bleeding. CONCLUSIONS: Patients carrying the ABCB1 wild-type genotype (CC) had a higher rate of severe perioperative bleeding compared with patients carrying the variant genotype (CT or TT). Discontinuation of clopidogrel 5 days or less before surgery and the ABCB1 wild-type genotype (CC) were independent risk factors for severe perioperative bleeding.

Effect of Body Mass Index on Posttonsillectomy Hemorrhage.

OBJECTIVE: Obesity affects adverse outcomes in patients undergoing various surgeries. Tonsillectomy is one of the most common surgical procedures and posttonsillectomy hemorrhage (PTH) is the major complication in patients with tonsillectomy. However, the effect of body mass index (BMI) on posttonsillectomy bleeding episodes is not well known. This study aimed to assess the clinical association between obesity and PTH. METHODS: A total of 98 tonsillectomies were retrospectively reviewed. Patient charts were analyzed regarding demographic data and the indication for surgery. Patients with PTH were compared with uneventful cases. Patients were divided into three groups based on BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥ 25 and <30 kg/m2), and obese (≥30 kg/m2). RESULTS: PTH occurred in 13% of patients with normal weight, in 23.5% of patients with overweight, and in 50% patients with obesity. The occurrence of PTH was significantly higher in patients with obesity than in those with normal weight and overweight (p = 0.008). Multivariate analysis showed that obesity was a significant factor affecting the incidence of PTH after adjusting for confounding factors. CONCLUSIONS: Our findings suggest that the obese condition is independently associated with the incidence of PTH.

Arachidonic acid causes hidden blood loss-like red blood cell damage through oxidative stress reactions.

BACKGROUND: Hidden blood loss (HBL) often occurs in the prosthetic replacement for joint, but the mechanism is still not clear. MATERIALS AND METHODS: This study tried to establish an animal model of HBL by injecting arachidonic acid (AA) into the Sprague-Dawley rats. Different concentrations of AA were injected into the tail veins of the rats, and blood samples were collected before and after administration at 24, 48, and 72 h. A complete blood count was obtained by to find the hemoglobin (Hb) and red blood cell (RBC) count changes. The glutathione peroxidase (GSH-PX) and total superoxide dismutase (T-SOD) activities and hydrogen peroxide (H2O2) levels were detected. The morphological changes of erythrocyte were observed under a polarizing microscope. The absorbance values of the blood samples were tested to determine the presence of ferryl Hb. RESULTS: HBL occurred in the experimental groups when the concentration of AA reached 10 mmol/L; Hb and RBC values decreased sharply at 24- and 48-h postinjection. This was followed by reduced activities of GSH-PX and T-SOD and decreased levels of H2O2. Moreover, the pathologic changes of red cell morphology mainly presented as pleomorphic RBC morphology, including cell rupture. The absorbance values of the blood samples were in accordance with ferryl Hb features. RBC and Hb values were relatively stable at 72 h. The GSH-PX and T-SOD activities and H2O2 levels gradually increased up to a balanced state. CONCLUSIONS: The study concluded that high concentrations of AA can induce oxidative stress reactions in the body, causing acute injury of RBCs, which is closely related to HBL.

Prognostic factors of hemorrhagic complications after oxaliplatin-based hyperthermic intraperitoneal chemotherapy: Toward routine preoperative dosage of Von Willebrand factor?

BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. METHODS: A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5). RESULTS: Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94-1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5-94], p < 0.01) for predicting HC. CONCLUSIONS: Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.

PERSISTENT OVERPRODUCTION OF INTRAOCULAR VASCULAR ENDOTHELIAL GROWTH FACTOR AS A CAUSE OF LATE VITREOUS HEMORRHAGE AFTER VITRECTOMY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: The purpose of this study was to investigate whether vitreous levels of vascular endothelial growth factor (VEGF) predict late vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy, and how VEGF level changes in patients with postoperative late VH. METHODS: Eighty-five eyes of 68 patients with proliferative diabetic retinopathy who underwent vitrectomy were analyzed retrospectively. Vitreous samples were collected from eyes undergoing primary vitrectomy and from eyes with late VH undergoing second vitrectomy. Vitreous VEGF levels were measured using enzyme-linked immunosorbent assay. The relationship between VEGF level and late VH (>4 weeks) occurring during follow-up as well as clinical findings, and changes in VEGF level in eyes with late VH undergoing second vitrectomy were analyzed. RESULTS: Late VH occurred in 20 (24%) of 85 eyes, and 9 eyes required second vitrectomy. Vitreous levels of VEGF were significantly higher (median: 1,945 pg/mL; P < 0.0001) in eyes with late VH than in those without. Preexisting iris neovascularization (P < 0.0001), hypertension (P = 0.002), and proteinuria (P = 0.040) were also significant risk factors of late VH. Multivariate logistic regression analysis showed that a higher vitreous VEGF level was independently associated with a risk of postoperative late VH in patients with proliferative diabetic retinopathy (odds ratio: 20.8, 95% confidence interval: 2.72-159.47; P = 0.003). Vitreous VEGF level at second vitrectomy in patients with late VH was significantly lower compared with that at primary vitrectomy, but remained elevated (median: 1,610 pg/mL; P = 0.023). CONCLUSION: In patients with proliferative diabetic retinopathy, high intraocular VEGF level at primary vitrectomy was identified as an independent risk factor of postoperative late VH. Persistent overproduction of intraocular VEGF may be associated with postoperative late VH.

Bridge therapy or standard treatment for urgent surgery after coronary stent implantation: Analysis of 314 patients.

Intravenous administration of a short acting glycoprotein IIb/IIIa inhibitor has been proposed as a bridge to surgery in patients on dual antiplatelet treatment, but data in comparison with other treatment options are not available. We conducted a retrospective analysis of consecutive patients who underwent un-deferrable, non-emergency surgery after coronary stenting. The bridge therapy was performed after discontinuation of the oral P2Y12 inhibitor by using i.v. tirofiban infusion. Net Adverse Clinical Events (NACE) was the primary outcome. We analyzed 314 consecutive patients: the bridge strategy was performed in 87 patients, whereas 227 were treated with other treatment options and represent the control group. Thirty-day NACE occurred in 8% of patients in the bridge group and in 22.5% in the control group (p < 0.01). Bridge therapy was associated with decreased 30-day NACE rate [Odds ratio (OR) 0.30; 95% confidence interval (CI) 0.13-0.39; p < 0.01], particularly when the time interval between stenting and surgery was ≤ 60 days (OR 0.09, 95% CI 0.01-0.72; p = 0.02). There were no cases of stent thrombosis in the bridge group and 3 (1.3%) in the control group. Bridge therapy was associated with decreased events rates as compared to both patients with and without P2Y12 inhibitors discontinuation in the control group. After adjustment for the most relevant covariates, the favorable effect of the bridge therapy was not materially modified. In conclusion, perioperative bridge therapy using tirofiban was associated with reduced 30-day NACE rate, particularly when surgery was performed within 60 days after stent implantation.

[Effect of anxin granules combined with tirofiba on patients with acute myocardial infarction after elective percutaneous coronary intervention].

To investigate the influence of Anxin granules combined with tirofiban on acute myocardial infarction (AMI) Patients after elective percutaneous coronary intervention (PCI). One hundred and twenty AMI patients were randomly divided into treatment group and control group. The patients in the two groups were all given Tirofiban 30mins before PCI . The treatment group was added Anxin granules 30 mins before and after PCI. Tissue factor (TF) and von willebrand factor (vWF) were tested at 6 hours after operation. Syndromatology alteration of traditional Chinese medicine (TCM) and bleeding complications were observed at 4 weeks after operation. Both TF and vWF at 6 hours after operation of the treatment group was lower than the control group significantly (P < 0.01), while the condition of myocardial ischemia at 90 mins after operation of the treatment group was better than control group with significance. The syndromatology alteration of TCM especially spontaneous perspiration and hypodynamia of the treatment group were improved significantly compared to control group 4 weeks after operation. All patients in both groups had no bleeding complications and thrombopenia. The study suggests that Anxin granules combined with tirofiba can improve the clinical efficacy and the endothelial function of AMI patients after PCI with no increase in bleeding events.

Procalcitonin in the recognition of complications in critically ill surgical patients.

BACKGROUND: Procalcitonin (PCT) is a relatively new, promising indirect parameter for infection. In the intensive care unit (ICU) it can be used as a marker for sepsis. However, in the ICU there is a need for reliable markers for clinical deterioration in the critically ill patients. This study determines the clinical value of PCT concentrations in recognizing surgical complications in a heterogeneous group of general surgical patients in the ICU. MATERIAL AND METHODS: We prospectively collected PCT concentration data from April 2010 to June 2012 for all general surgical patients admitted to the ICU. Both the relationships between PCT levels and events (diagnostic and therapeutic interventions) as well as between PCT levels and surgical complications (abscesses, bleeding, perforation, ischemia, and ileus) were studied. RESULTS: PCT concentrations were lower in patients who developed complications than those who did not develop complications on the same day, although not significant (P = 0.27). A 10% increase in PCT levels resulted in a 2% higher complication odds, but again this was not significant (odds ratio [OR], 1.020; 95% confidence interval [CI], 0.961-1.083; P = 0.51). Even a 20% or 30% increase in PCT concentrations did not result in higher complication probability (OR, 1.039; 95% CI, 0.927-1.165 and OR, 1.057; 95% CI, 0.897-1.246). Furthermore, an increase in PCT levels did not show an increase or a reduction in the number of diagnostic and therapeutic interventions. CONCLUSIONS: An increase in PCT levels does not help to predict surgical complications in critically ill surgical patients.

Population pharmacokinetics of tranexamic acid in paediatric patients undergoing craniosynostosis surgery.

BACKGROUND: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements during craniofacial surgery. The pharmacokinetics of TXA have not been fully characterized in paediatric patients and dosing regimens remain diverse in practice. A mixed-effects population analysis would characterize patient variability and guide dosing practices. OBJECTIVE: The objective of this study was to conduct a population pharmacokinetic analysis and develop a model to predict an effective TXA dosing regimen for children with craniosynostosis undergoing cranial remodelling procedures. METHODS: The treatment arm of a previously reported placebo-controlled efficacy trial was analysed. Twenty-three patients with a mean age 23 ± 19 months received a TXA loading dose of 50 mg/kg over 15 min at a constant rate, followed by a 5 mg/kg/h maintenance infusion during surgery. TXA plasma concentrations were measured and modelled with a non-linear mixed-effects strategy using Monolix 4.1 and NONMEM(®) 7.2. RESULTS: TXA pharmacokinetics were adequately described by a two-compartment open model with systemic clearance (CL) depending on bodyweight (WT) and age. The apparent volume of distribution of the central compartment (V1) was also dependent on bodyweight. Both the inter-compartmental clearance (Q) and the apparent volume of distribution of the peripheral compartment (V2) were independent of any covariate. The final model may be summarized as: CL (L/h) = [2.3 × (WT/12)(1.59) × AGE(-0.0934)] × e(η1), V1 (L) = [2.34 × (WT/12)(1.4)] × e(η2), Q (L/h) = 2.77 × e(η3) and V2 (L) = 1.53 × e(η4), where each η corresponds to the inter-patient variability for each parameter. No significant correlation was found between blood volume loss and steady-state TXA concentrations. Based on this model and simulations, lower loading doses than used in the clinical study should produce significantly lower peak concentrations while maintaining similar steady-state concentrations. CONCLUSIONS: A two-compartment model with covariates bodyweight and age adequately characterized the disposition of TXA. A loading dose of 10 mg/kg over 15 min followed by a 5 mg/kg/h maintenance infusion was simulated to produce steady-state TXA plasma concentrations above the 16 µg/mL threshold. This dosing scheme reduces the initial high peaks observed with the larger dose of 50 mg/kg over 15 min used in our previous clinical study.

Efficacy and safety of early versus late glycoprotein IIb/IIIa inhibitors for PCI.

BACKGROUND: Glycoprotein (Gp) IIb/IIIa inhibitors are beneficial for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). However, optimal drug timing remains inconclusive. Therefore, this study was to perform a meta-analysis of the clinical efficiency and safety of early versus late GpIIb/IIIa inhibitors in STEMI patients undergoing PCI. METHODS: A comprehensive search was to identify randomized trials of early versus late GpIIb/IIIa inhibitors in STEMI patients undergoing PCI. The GpIIb/IIIa inhibitors were abciximab and small-molecular Gp inhibitors (SMGP) namely eptifibatide and tirofiban. The efficacy endpoints included pre-procedural Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, post-procedural TIMI 3 flow, complete ST-segment resolution, left ventricle ejection fraction (LVEF), and mortality. The safety endpoint was the occurrence of major bleeding complications. RESULTS: Nineteen trials were included in the meta-analysis, involving 4209 patients (early 2124 versus late 2085). Early GpIIb/IIIa inhibitors significantly improved pre-procedural TIMI 3 flow, while early abciximab, but not SMGP, further enhanced post-procedural TIMI 3 flow, complete ST-segment resolution, LVEF, and reduced six-month mortality. In addition to clopidogrel loading, only early abciximab improved pre-procedural TIMI 3 flow and complete ST-segment resolution. The rate of major bleeding complications was not increased in early GpIIb/IIIa inhibitors with/without clopidogrel loading. CONCLUSIONS: Early GpIIb/IIIa inhibitors improved pre-procedural TIMI 3 flow and early abciximab provided favorable clinical outcomes in STEMI patients undergoing PCI. On the basis of clopidogrel loading, early abciximab enhanced pre-procedural TIMI 3 flow and ST-segment resolution. These beneficial effects were achieved without increased risks of major bleeding complications.

Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice.

AIM: To investigate the effect of matrix metalloproteinase-9 (MMP-9) on the remnant liver after massive hepatectomy in the mouse. METHODS: Age-matched, C57BL/6 wild-type (WT), MMP-9(-/-), and tissue inhibitors of metalloproteinases (TIMP)-1(-/-) mice were used. The mice received 80%-partial hepatectomy (PH). Samples were obtained at 6 h after 80%-PH, and we used histology, immunohistochemical staining, western blotting analysis and zymography to investigate the effect of PH on MMP-9. The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor. RESULTS: We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis. There were significantly fewer and smaller hemorrhagic and necrotic lesions in MMP-9(-/-) remnant livers compared with WT and TIMP-1(-/-) livers (P < 0.01), with no difference between WT and TIMP-1(-/-) mice. Serum alanine aminotransaminase levels were significantly lower in MMP-9(-/-) mice compared with those in TIMP-1(-/-) mice (WT: 476 ± 83 IU/L, MMP-9(-/-): 392 ± 30 IU/L, TIMP-1(-/-): 673 ± 73 IU/L, P < 0.01). Western blotting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9(-/-) mice, which was in contrast to WT and TIMP-1(-/-) mice. No change in MMP-2 expression was observed in any of the study groups. Similar to MMP-9(-/-) mice, when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001, hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice (P < 0.05). These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver. CONCLUSION: Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and might be a potential therapy to ameliorate liver injury after massive hepatectomy.

Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart.

Unexplained bleeding episodes are associated with ventricular assist devices (VAD) and can occur in part due to acquired von Willebrand syndrome (AVWS). AVWS is characterised by loss of high molecular weight (HMW) multimers of von Willebrand factor (VWF) and decreased ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. Loss of multimers can occur as VWF is subjected to increased shear stress, which occurs in presence of VADs. We studied 12 patients who required mechanical support of their native heart for terminal cardiac insufficiency. Nine patients underwent placement of a VAD, while three underwent placement of a total artificial heart (TAH), which is connected directly to heart and large cardiac vessels without cannulas. Within one day of VAD implantation, four of five patients evaluated demonstrated loss of HMW multimers and impaired VWF function. AVWS was present within two weeks of implantation in eight of nine patients, and in all seven tested patients after >/=3 months. Patients with different VAD types developed varying severities of AVWS. After VAD explantation, HMW multimers were detectable and VWF function normalised in all patients. AVWS was not observed in the TAH patients studied. Our findings demonstrate that patients with an implanted VAD experience a rapid onset of AVWS that is quickly and completely reversed after device explantation. In addition, TAH patients do not develop AVWS. These results suggest that shear stress associated with exposure of blood to VAD cannulas and tubes may contribute to the development of AVWS.

Heparin-like effect in liver disease and liver transplantation.

Liver cirrhosis is characterized by impairment of primary and secondary hemostasis but it is not clear how this impairment is related to the bleeding problems seen in cirrhosis. This delicate hemostatic balance can be perturbed by numerous conditions, such as variceal bleeding, renal failure, or infection/sepsis, which may lead to worsening of coagulation status to date. The role of endogenous heparinoids (glycosaminoglycans) in the coagulopathy of patients who have cirrhosis has been demonstrated by thromboelastography with the addition of heparinase I in patients who have recent variceal bleeding and infection. The heparin-like effect has also been demonstrated to be part of the coagulopathy seen after reperfusion in patients who have cirrhosis and are undergoing liver transplant. Therapeutic implications of these findings are not clear at the moment and the use of drugs able to cleave heparinoids should be explored.

Severe secondary postpartum hemorrhage 3 weeks after cesarean section: alternative etiologies of uterine scar non-union.

A case of secondary postpartum hemorrhage that occurred 3 weeks after cesarean section requiring total abdominal hysterectomy is reported. The patient's history and pathologic features of the removed uterus did not allow the authors to clearly recognize a previous reported cause of this potentially life-threatening complication. Alternative causes of the non-union of the uterine incision are suggested.

Role of p38 mitogen-activated protein kinase pathway in estrogen-mediated cardioprotection following trauma-hemorrhage.

p38 mitogen-activated protein kinase (MAPK) activates a number of heat shock proteins (HSPs), including HSP27 and alpha(B)-crystallin, in response to stress. Activation of HSP27 or alpha(B)-crystallin is known to protect organs/cells by increasing the stability of actin microfilaments. Although our previous studies showed that 17beta-estradiol (E(2)) improves cardiovascular function after trauma-hemorrhage, whether the salutary effects of E(2) under those conditions are mediated via p38 MAPK remains unknown. Male rats (275-325 g body wt) were subjected to soft tissue trauma and hemorrhage (35-40 mmHg mean blood pressure for approximately 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were injected intravenously with vehicle, E(2) (1 mg/kg body wt), E(2) + the p38 MAPK inhibitor SB-203580 (2 mg/kg body wt), or SB-203580 alone, and various parameters were measured 2 h thereafter. Cardiac functions that were depressed after trauma-hemorrhage were returned to normal levels by E(2) administration, and phosphorylation of cardiac p38 MAPK, HSP27, and alpha(B)-crystallin was increased. The E(2)-mediated improvement of cardiac function and increase in p38 MAPK, HSP27, and alpha(B)-crystallin phosphorylation were abolished with coadministration of SB-203580. These results suggest that the salutary effect of E(2) on cardiac function after trauma-hemorrhage is in part mediated via upregulation of p38 MAPK and subsequent phosphorylation of HSP27 and alpha(B)-crystallin.

Hemispherectomy procedures in children: haematological issues.

OBJECTS: In literature, excessive perioperative haemorrhage and related haemodynamic instability have been described as major risk factors in hemispherectomy. In this report we analyse the impact of neurosurgical operation on both the haematological and coagulative patterns of these children, especially focusing on younger patients. METHODS: From 1993 to 2003, 18 consecutive children suffering from intractable epilepsia and treated by hemispherectomy were admitted to the Pediatric Intensive Care Unit (PICU) of Catholic University Medical School, Policlinico Gemelli, Rome. Eight children had an entire hemisphere removed (anatomical hemispherectomy), whereas the remaining 10 underwent disconnective procedures (functional hemispherectomy) or cerebral cortex ablations (e.g. hemicorticectomy). Eleven out of these 18 children underwent hemispherectomy because of hemimegalencephaly (HME): their mean age was 14.5 months (range 3-56 months); non-HME patients underwent surgery for epileptogenic lesions involving the cerebral hemisphere to a great extent or diffusely. Data have been compared with an historical cohort of 13 children operated on before 1992 at the same institution comparable for age, aetiology of epilepsy and the modalities of surgical operation. CONCLUSIONS: Blood losses and haemotransfusions showed a profound influence on the haematologic/coagulative status of the children operated upon. A strict correlation was demonstrated between estimated red cell volume (ERCV) loss and haemostatic impairment in this series. Recent surgical techniques appear to reduce blood losses and related haemocoagulative risks even in younger patients.