Biomedical subjects

U Martinowitz

Publications and source records attributed to U Martinowitz.

At least 19 recordsLinked to original sources

PubMed2006

Hepatitis C at the israeli national hemophilia center.

Haemophilia patients who received non-virucidally treated large pool clotting factors before 1987 have a high rate of chronic hepatitis C viral infection (HCV). Some patients are coinfected with HIV. Haemophilia patients and other coagulation disorders were treated at one centre since the beginning of the 1970, and the Israeli National Hemophilia Center (INHC) was officially founded in 1987. To characterize patients with HCV as well as patients with HCV/HIV coinfection at the INHC. Patients with haemophilia and other coagulation disorders positive for HCV antibodies were evaluated between 2001 and 2004. Demographic data, type and severity of coagulation disorder, frequency of coagulation factor usage and treatment with concentrated clotting factors prior to 1987 were recorded. Liver enzymes, viral load, genotype and data supporting advanced liver disease were evaluated. About 179 of 239 haemophilia patients (75%) tested positive for anti-HCV antibodies. Our cohort consisted of 165 patients in whom clinical, biochemical and virological data were available. About 117 patients had active HCV infection with HCV-RNA-positive, and 27 were HCV/HIV coinfected. Twenty-one patients (13%) persistently tested HCV-RNA-negative, hence were considered to clear their HCV infection. There was no former USSR immigrants among HCV/HIV coinfected compared with HCV-infected or HCV-RNA-negative groups (0 vs. 30% and 38%, respectively; P < 0.001). HCV-RNA-negative patients used concentrated coagulation factor less frequently than HCV or HCV/HIV-infected patients (48% vs. 73%; P = 0.023, and 48% vs. 74%; P = 0.043, respectively). The use of concentrated clotting factors before 1987 was significantly more frequent in HCV/HIV than in either HCV-infected or HCV-RNA-negative patients (96% vs. 49% and 48%, respectively; P < 0.001). Compared with HCV/HIV subjects, patients with HCV monoinfection were characterized by a higher proportion of infection with genotype 1 (80% vs. 61%; P = 0.027). The rate of persistently normal liver enzymes in these patients was higher (24% vs. 7%; P = 0.05) than in the HCV/HIV-coinfected patients. Advanced liver disease was significantly more common in patients with HCV/HIV-coinfection than in HCV-monoinfected patients (11% vs. 3%; P = 0.045). The majority of haemophilia patients are infected with HCV. Viral clearance occurred in a minority of these patients. HCV monoinfected and HCV/HIV coinfected differ clinically and prognostically.

Adolescent↗

PubMed2006

Non-invasive biomarkers of liver fibrosis in haemophilia patients with hepatitis C: can you avoid liver biopsy?

Liver biopsy remains the gold standard for the evaluation of fibrosis despite its risks and limitations, especially in haemophilia patients. Recently, non-invasive biomarkers have been used to assess histological features. The most thoroughly evaluated biomarker is the FibroTest (FT) (AUROC 0.80 for fibrosis stages F2F3F4 vs. F0F1). To estimate liver fibrosis in haemophilia patients infected with hepatitis C (HCV) using non-invasive biomarkers without liver biopsy. One hundred and thirty-two haemophilia patients (124 male, mean age 38 +/- 14 years) with anti-HCV antibodies were evaluated. These patients were stratified into several groups: patients with features of advanced liver disease - seven, persistently HCV RNA-negative - 21, persistently normal liver function tests (LFTs)- 24, HCV/HIV co-infected - 27. The following biomarkers of fibrosis were used: FT, AST-to-platelet ratio index (APRI), Forns index, age-platelet index and hyaluronic acid. The obtained scores were correlated with the clinical features of the patients. Estimated by the FT, the distribution of the stage of fibrosis in the 132 patients was F0F1 = 65% (86/132), F2 = 5% (7/132), F3 = 13% (17/132) and F4 = 17% (22/132). Using FT, all patients with clinical suspicion of advanced liver disease were classified as F3F4, whereas patients with persistently HCV RNA-negative were all classified as F0F1. Twenty-one per cent (5/24) of the patients with persistently normal LFTs had fibrosis stage F3F4. The proportion of F3F4 among HCV/HIV co-infected patients was significantly higher than among HCV mono-infected (52% vs. 33%; P = 0.05). Concordance of three or more biomarkers was present in 43% (57/132) of the patients. Liver biopsy could be avoided in 70% (92/132) using a practical assumption that if FT is in concordance with APRI and/or Forns, then we may confidently rely on the biomarker. Concordance rate for patients with presumably advanced or minimal liver disease was excellent (100% and 95% respectively). In our HCV-infected haemophilia patients, FT correctly identified clinically advanced or minimal liver disease. Discordance among the various biomarkers of fibrosis was considerate; nevertheless, practical combination of FT, APRI, and Forns may predict stage of fibrosis with accuracy, potentially avoiding liver biopsy in the majority of the patients.

Adult↗

PubMed2006

Surgical excision of a giant pelvic pseudotumour in a patient with haemophilia A.

The development of pseudotumors represents one of the most challenging complications facing physicians who care for patients with hemophilia. The successful removal of the giant pseudotumor described in this case report was achieved by a multidisciplinary team and demonstrates that this approach, albeit associated with significant risk, may be curative.

Abdomen↗

PubMed2006

Prerequisites for recombinant factor VIIa-induced thrombin generation in plasmas deficient in factors VIII, IX or XI.

BACKGROUND: Recombinant factor VIIa (rFVIIa) used for the treatment of hemophilia A or B patients with an inhibitor is hemostatically effective because it induces thrombin generation (TG), despite grossly impaired FVIII- and FIX-dependent amplification of FX activation. Tissue factor (TF) and or activated platelets were shown to be essential for the rFVIIa activity. OBJECTIVE: To evaluate the relative effects of TF and phospholipids on rFVIIa-induced TG in FVIII-, FIX- and FXI-deficient plasmas. METHODS: Phospholipids had an independent effect that was augmented by TF. The contribution of blood-borne TF in FVIII-, FIX- and FXI-deficient plasma to rFVIIa-induced TG was demonstrated by removing microparticles and use of anti-TF antibodies. RESULTS: At increasing concentrations of rFVIIa, the dependence of rFVIIa-induced TG on TF declined, but the presence of phospholipids was essential. rFVIIa was also shown to activate purified FIX and FX in the presence of phospholipids and absence of TF. rFVIIa-induced TG was dramatically augmented in FVIII- or FIX-deficient plasma in which the level of FVIII or FIX was increased to 1 or 2 U dL(-1). CONCLUSIONS: The data indicate that rFVIIa-induced TG is affected by TF, phospholipids, rFVIIa concentration, and the presence of FVIII and FIX.

Blood Platelets↗

PubMed2006

Platelet function of newborns as tested by cone and plate(let) analyzer correlates with gestational Age.

UNLABELLED: The issue of platelet function in infants and neonates is of interest, and current data are debatable. A new method for assessing platelet function involves using the cone and plate(let) analyzer (CPA), applicable for small (0.2 ml) whole blood volumes. We used polystyrene surface-coated plates to evaluate cord blood neonatal platelet function under flow. One hundred and sixty full-term and 29 preterm infants born at the Sheba Medical Center between March 2003 and January 2004 were evaluated for platelet adhesion measured as surface coverage (SC; the percentage of total area covered by platelets) and platelet aggregation, defined as the average size (AS) of the aggregates. Platelets from preterm infants displayed less platelet adhesion than did those from full-term infants. Platelet SC correlated with gestational age in all infants (p < 0.05), and both groups exhibited similar aggregation (AS). AS values, however, were significantly lower than the normal adult range in our laboratory. Infants born to mothers with pregnancy-induced hypertension displayed significantly lower SC. No association was found between CPA and postnatal complications. CONCLUSION: CPA provides a rapid, feasible option for testing platelet function in neonates. Its potential predictive value deserves further attention, and more extensive studies are warranted.

Adult↗

PubMed2005

Bone properties and muscle strength of young haemophilia patients.

PURPOSE: To evaluate bone properties, muscle strength and the relationship between the two, in young (7.0-17.7 years) haemophilia patients (h) and healthy boys (c). SUBJECTS: Twenty-seven boys with severe haemophilia and 33 healthy boys, of similar age, body mass, height, (mean +/- sd for h and c, respectively: 11.2 +/- 3.2 vs. 11.4 +/- 2.9 years, 42.6 +/- 16.6 vs. 41.6 +/- 17.3 kg, 145 +/- 18 vs. 146 +/- 17 cm) and pubertal stage according to secondary sex characteristics, volunteered for the study. all subjects were physically inactive (as determined by questionnaire). METHODS: Subjects performed isokinetic elbow and knee extension and flexion tests at two angular velocities (biodex system ii dynamometer). Bone properties were evaluated by qualitative ultrasound (sunlight omnisense), at the distal radius and tibial mid-shaft. H subjects received prophylactic factor viii treatment within the 24 h preceding testing. No test was performed in the presence of haemorrhage. RESULTS: Muscle strength was consistently higher in c compared with h, especially in the lower limbs (e.g. knee extension: 1.80 +/- 0.44 vs 1.48 +/- 0.53 N x m x kg(-1) body mass, respectively, p = 0.01). No differences were observed in tibial or radial speed of sound between groups. Correlations between muscle strength and bone properties were observed only in the lower limbs and only in c (r = 0.37-0.48). CONCLUSION: Muscle strength, especially lower limbs' strength, was lower in haemophilia patients compared with a matched, similarly inactive population of healthy boys. Nevertheless, at this age range, this relative weakness is not associated with inferior bone properties.

Adolescent↗

PubMed2005

Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force.

BACKGROUND: Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. OBJECTIVES: The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines. METHODS: A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. RESULTS: Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%-57%). CONCLUSIONS: As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses.

Adolescent↗

PubMed2004

Yttrium synoviorthesis of the elbow joints in persons with haemophilia.

Yttrium has been used as the material of choice for synoviorthesis in our centre since 1984. An audit was carried out to determine the long-term results of this modality for treating elbow joints. An unacceptably high percentage of patients lost range-of-movements in the articulation treated. Good results were achieved with respect to a reduction in the bleeding incidences. It is suggested that another isotope be utilized and that other centres carry out an audit and publish their data.

Elbow Joint↗

PubMed2003

A new approach to treatment of bleeding episodes in young hemophilia patients: a single bolus megadose of recombinant activated factor VII (NovoSeven).

Recombinant activated factor VII (rFVIIa, NovoSeven) represents an effective treatment for hemophilia patients with inhibitors, but no consensus as to the best dosing regimen exists. We assessed the efficacy and safety of a rFVIIa 'megadose' (300 micro g kg(-1) bolus) as treatment for bleeds in three young inhibitor patients. Of 114 bleeds, 95 responded to a single dose. Pain relief was faster and therapy duration significantly shorter than with continuous infusion (CI) regimens or standard boluses (90 micro g kg(-1) every 3 h). Rebleeding occurred in 9.6% of cases and 19/114 episodes required a second bolus injection. Although rFVIIa consumption per bleed (median: 300 micro g kg(-1)) was higher than with standard boluses (180-270 micro g kg(-1)), patients found single bolus administration more convenient than recurrent injections or CI. With two exceptions, no complications occurred within 3 h of treatment, despite high FVII:C levels (median: 27.4 U mL(-1); range: 19.8-54 U mL(-1)). Treatment of bleeds with a rFVIIa megadose in young inhibitor patients is effective and well tolerated.

Adult↗

PubMed2002

Treatment of obstetric hemorrhage with recombinant activated factor VII (rFVIIa).

Recombinant activated factor VII (rFVIIa, NovoSeven) was used in three patients with massive obstetric hemorrhage due to placenta previa accreta, rupture of the uterus and pre-eclampsia with HELLP. Administration of the drug markedly decreased the bleeding and enabled control of the hemorrhage. rFVIIa seems to be an adjunctive hemostatic measure for the treatment of severe obstetric hemorrhage.

Blood Transfusion↗

PubMed2002

Continuous infusion of coagulation factors.

UNLABELLED: Continuous infusion (CI) of coagulation factor concentrate is aimed at maintaining a steady haemostatic level of the missing factor in circulation, preventing dangerous troughs below the haemostatic level and unnecessary high peaks, which increase the safety and decrease the consumption of factor concentrate replacement therapy. This can be achieved by the administration of the coagulation factor at a rate corresponding to its elimination. CI has been used in wider extent since the early 1990s, after the resolution of basic questions such as the stability of factor concentrates after reconstitution, the risk of contamination and bacterial overgrowth in these biological materials during either preparation of infusion bags or prolonged administration, the frequent local thrombophlebitis, the knowledge of pharmacokinetics of coagulation factors in the conditions of CI and the development of adequate minipumps. The increasing clinical experience with CI used in haemophilia A and B and von Willebrand disease has proven the advantages of this mode of replacement therapy, providing improved margins of efficacy and safety in various clinical settings requiring the maintenance of haemostatic levels over prolonged periods, as well as reduction in treatment cost compared with the traditional therapy via intermittent injections of coagulation factors. KEYWORDS: continuous infusion, factor VIII, factor IX, haemophilia, recombinant FVIIIa, von willebrand disease.

Blood Coagulation Factors↗

PubMed2002

Efficacy and safety of a factor VIII-von Willebrand factor concentrate 8Y: stability, bacteriological safety, pharmacokinetic analysis and clinical experience.

The present study was undertaken to evaluate stability, pharmacokinetic profile and efficacy of continuous infusion of 8Y in patients with different types of von Willebrand disease (vWD). Following reconstitution, 8Y levels of von Willebrand factor ristocetin cofactor (vWF:Rco), vWF antigen and factor VIII coagulant activity (FVIII:C) decreased to about 80% of the baseline levels; addition of low molecular weight heparin decreased the level of FVIII:C even further. Reconstituted 8Y was found to be sterile for up to 6 days postreconstitution. Ten vWD patients (four with type 2A, three with type 3, two with type 1 and one with 2N) underwent pharmacokinetic analysis. The recovery of vWF: RCo was significantly lower in patients with type 3 vWD (1.4 +/- 0.05% U(-1) kg(-1)) compared with that of the patients with types 1 (2.3 +/- 0.52% U(-1) kg(-1)) or 2A (2.0 +/- 0.06% U(-1) kg(-1)) vWD (P = 0.015). Type 3 vWD patients exhibited significantly higher vWF:RCo clearance (5.1 +/- 1.1 mL kg(-1) h(-1)) compared with that of patients with type 2A (2.8 +/- 0.7 mL kg(-1) h(-1)) and type 1 (2.6 +/- 1.0 mL kg(-1) h(-1)) vWD (P = 0.028). Accordingly, terminal half-life was lower in patients with type 3 vWD (8.0 +/- 0.6 h(-1)) compared with type 2A (12.7 +/- 5.9 h(-1)) or type 1 (14 +/- 1.2 h(-1)) vWD patients. Multimeric pattern of vWF from patients' plasma was similar to that of 8Y. In two patients treated with 8Y by continuous infusion for prevention or treatment of bleeding haemostasis was achieved. Thus, 8Y is suitable and haemostatically effective for continuous infusion treatment in patients with vWD.

Adult↗

PubMed2001

Synoviorthesis with radioactive Yttrium in haemophilia: Israel experience.

Radioactive Yttrium-90 (90Y) was injected into 163 joints. Of these patients 115 were persons with haemophilia and they suffered from recurrent haemarthroses. The median age at the time of the initial exposure to 90Y was between 11 and 15 years and the median follow-up period 11 years. Over 80% of the patients with haemophilia reported a decrease in the number of haemarthroses and 15% stopped bleeding altogether in the treated articulation. The safety of this modality of management has been reported and hence the patients age should not be regarded as a criteria.

Adolescent↗

PubMed2001

Dental extractions in patients maintained on oral anticoagulant therapy: comparison of INR value with occurrence of postoperative bleeding.

The purpose of this study was to evaluate the incidence of postoperative bleeding in patients treated with oral anticoagulant medication who underwent dental extractions without interruption of the treatment and to analyze the incidence of postoperative bleeding according to the International Normalized Ratio (INR) value. The 249 patients who underwent 543 dental extractions were divided into five groups: Group 1 with INRs of 1.5-1.99, Group 2 with INRs of 2-2.49, Group 3 with INRs of 2.5-2.99, Group 4 with INRs of 3-3.49 and Group 5 with INRs>3.5. The INR was measured on the day of the procedure. Local haemostasis was carried out with gelatin sponge and multiple silk sutures. Of the 249 patients, 30 presented with postoperative bleeding (12%): Group 1, three patients presented with bleeding (5%), Group 2, 10 patients (12.8%), Group 3, nine patients (15.2%), Group 4, five patients (16.6%) and Group 5, three patients (13%). The incidence of postoperative bleeding was not significantly different among the five groups. The value of the INR at the therapeutic dose did not significantly influence the incidence of postoperative bleeding. Thus, dental extractions can be performed without modification of oral anticoagulant treatment. Local haemostasis with gelatin sponge and sutures appears to be sufficient to prevent postoperative bleeding.

Administration, Oral↗

PubMed2001

Intravenous rFVIIa administered for hemorrhage control in hypothermic coagulopathic swine with grade V liver injuries.

BACKGROUND: Intravenous administration of recombinant activated human clotting factor VII (rFVIIa) has been used successfully to prevent bleeding in hemophilia patients undergoing elective surgery, but not in previously normal trauma patients. This study was conducted to determine whether rFVIIa was a useful adjunct to gauze packing for decreasing blood loss from grade V liver injuries in hypothermic and coagulopathic swine. METHODS: All animals (n = 10, 35 +/- 2 kg) underwent a 60% isovolemic exchange transfusion with 6% hydroxyethyl starch and were cooled to 33 degrees C core temperature. The swine then received a grade V liver injury and 30 seconds later, either 180 microg/kg rFVIIa, or saline control. All animals were gauze packed 30 seconds after injury and resuscitated 5.5 minutes after injury with lactated Ringer's solution to their preinjury mean arterial pressure. Posttreatment blood loss, mean arterial pressure, resuscitation volume, and clotting studies were monitored for 1 hour. Histology of lung, kidney, and small bowel were obtained to evaluate for the presence of microvascular thrombi. RESULTS: At the time of injury, core temperature was 33.3 degrees +/- 0.4 degrees C, hemoglobin was 6 +/- 0.7 g/dL, prothrombin time was 19.1 +/- 1.0 seconds, activated partial thromboplastin time was 29.0 +/- 4.8 seconds, fibrinogen was 91 +/- 20 mg/dL, and platelets were 221 +/- 57 x 105/mL, with no differences between groups (p > 0.05). Clotting factor levels confirmed a coagulopathy at the preinjury point. The posttreatment blood loss was less (p < 0.05) in group 1 (527 +/- 323 mL), than in group 2 (976 +/- 573 mL). The resuscitation volume was not different (p > 0.05). One-hour survival in both groups was 100%. Compared with the control group, rFVIIa increased the circulating levels of VIIa and, despite hypothermia, shortened the prothrombin time 5 minutes after injection (p < 0.05). Laboratory evaluation revealed no systemic activation of the clotting cascade. Postmortem evaluation revealed no evidence of large clots in the hepatic veins or inferior vena cava, or microscopic thrombi in lung, kidney, or small intestine. CONCLUSION: rFVIIa reduced blood loss and restored abnormal coagulation function when used in conjunction with liver packing in hypothermic and coagulopathic swine. No adverse effects were identified.

Animals↗

PubMed2001

Recombinant activated factor VII for adjunctive hemorrhage control in trauma.

BACKGROUND: Recombinant activated factor VII (rFVIIa) was approved for treatment of hemorrhages in patients with hemophilia who develop inhibitors to factors VIII or IX. Conditions with increased thromboembolic risk, including trauma with or without disseminated intravascular coagulation, were considered a contraindication for the drug. The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. Therefore, use of the drug in trauma patients suffering uncontrolled hemorrhage appears to be rational. METHODS: Seven massively bleeding, multitransfused (median, 40 units [range, 25-49 units] of packed cells), coagulopathic trauma patients were treated with rFVIIa (median, 120 microg/kg [range, 120-212 microg/kg]) after failure of conventional measures to achieve hemostasis. RESULTS: Administration of rFVIIa resulted in cessation of the diffuse bleed, with significant decrease of blood requirements to 2 units (range, 1-2 units) of packed cells (p < 0.05); shortening of prothrombin time and activated partial thromboplastin time from 24 seconds (range, 20-31.8 seconds) to 10.1 seconds (range, 8-12 seconds) (p < 0.005) and 79 seconds (range, 46-110 seconds) to 41 seconds (range, 28-46 seconds) (p < 0.05), respectively; and an increase of FVII level from 0.7 IU/mL (range, 0.7-0.92 IU/mL) to 23.7 IU/mL (range, 18-44 IU/mL) (p < 0.05). Three of the seven patients died of reasons other than bleeding or thromboembolism. CONCLUSION: The results of this report suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure, in addition to surgical hemostatic techniques, and provides the motivation for controlled animal and clinical trials.

Adolescent↗

PubMed2000

Molecular analysis of the genotype-phenotype relationship in factor VII deficiency.

Factor VII (FVII) deficiency is a rare haemorrhagic condition, normally inherited as an autosomal recessive trait, in which clinical presentation is highly variable and correlates poorly with laboratory phenotype. The FVII (F7) gene was sequenced in 48 unrelated individuals with FVII deficiency, yielding a total of 23 novel lesions including 15 missense mutations, 2 micro-deletions, 5 splice junction mutations and a single base-pair substitution in the 5' untranslated region. Family studies were performed in order to distinguish the contributions of individual mutant F7 alleles to the clinical and laboratory phenotypes. Specific missense mutations were evaluated by molecular modelling in the context of the FVIIa-tissue factor crystal structure. Single base-pair substitutions in splice sites and the 5' untranslated region were studied by in vitro splicing assay and luciferase reporter gene assay, respectively. All probands were also typed for four previously reported F7 polymorphisms. In the majority of cases of FVII deficiency studied here, consideration of both mutational and polymorphism data permitted the derivation of plausible explanations for the FVII activity and antigen levels measured in the laboratory. Inter-familial variation in FVII activity and the antigen levels of heterozygous relatives of probands was found to be significantly higher than intra-familial variation, consistent with the view that the nature of the F7 gene lesion(s) segregating in a given family is a prime determinant of laboratory phenotype. Although no relationship could be discerned between laboratory phenotype and polymorphism genotype, the frequencies of the A2 and M2 polymorphic alleles were significantly higher in the FVII-deficient individuals tested than in controls. This suggests that the presence of these alleles may have served to increase the likelihood of pathological F7 gene lesions coming to clinical attention.

5' Untranslated Regions↗

PubMed2000

Intermittent injections vs. continuous infusion of factor VIII in haemophilia patients undergoing major surgery.

Continuous infusion (CI) of factor VIII (FVIII) has been proved to be a safe alternative to intermittent bolus injections (BI) in haemophilia A. Most reports on CI suggest a considerable saving in FVIII compared with historical controls treated with BI, but some recent reports failed to demonstrate such an effect. The present study prospectively compared safety, efficacy and factor requirements in 43 major surgical procedures performed in severe haemophilia A patients who were treated with either BI (18 operations) or CI (25 operations). The aim was to maintain factor VIII levels above the same minimum levels. Improved safety of CI over BI was observed, despite a bias in favour of the BI group (all underwent unilateral operations, compared with 24% of the CI group who underwent bilateral operations). Higher nadir levels were found in the CI group (0.44 +/- 0.06 vs. 0.31 +/- 0.09 IU/ml; P < 0.01) with a lower incidence of dangerous drops below 0.3 IU/ml (8% vs. 44% of patients respectively; P < 0.01), and a lower drop in haemoglobin (Hb) (1.56 +/- 1.21 vs. 3.01 +/- 2.13 g/dl; P < 0.05) and blood transfusion requirements (12% vs. 39%; P < 0.01). Major bleeding complications developed in three out of 18 patients (17%) in the BI group and none of the CI group (P = 0.06). The FVIII dosage was lower by 36% in the CI group (467 +/- 104 vs. 733 +/- 126 IU/kg; P < 0.01). Had the trough factor levels been maintained at the target levels, a greater difference of 72% would probably have been observed.

Adult↗