bluuebunny/crossref_metadata_2025 huggingface dataset:
An assessment of the learning curve for laparoscopic and total laparoscopic hysterectomy
Authors: B. Rosen David M. , Cario Gregory M. , Carlton Mark A. , Lam Alan M. , Chapman Michael
Published: March 2003

Objective

To determine guidelines for an appropriate learning curve for laparoscopic hysterectomy for novice and experienced surgeons.

Design

An analysis of the first year of practice, of an experienced laparoscopic surgeon, with a new technique for total laparoscopic hysterectomy, and of the initial year of training for an inexperienced laparoscopic surgeon.

Subjects

33 patients (group 1) underwent total laparoscopic hysterectomy (TLH) performed by an experienced gynaecological laparoscopic surgeon (G.C.), and 21 patients (group 2) underwent laparoscopic hysterectomy (LH) performed by a trainee surgeon (D.R.) under the supervision of one of the experienced surgeons.

Main outcome measures

Time for surgery, and peri‐ and postoperative complications were prospectively assessed and analysed as markers of completed learning of the techniques. Correlations between duration of surgery and uterine weight, patient weight, and history of previous abdominal surgery were also sought.

Results

Over the first year the time for the TLH was reduced from 145 min to 80 min (average time 99 min). A plateau for operating time was reached rapidly, at around 10 cases. There were only three minor complications in this group, two of which occurred in the first 10 patients. The time for the trainee surgeon was reduced from 180 min to 105 min during the first year (average 145 min) with complications reported in case numbers 8, 10 and 15. No correlations between surgical time and uterine size, patient weight or history of previous surgery were detected.

Conclusion

The learning curve for laparoscopic hysterectomy for a trainee laparoscopic surgeon was seen to improve steadily, allowing unsupervised surgery after 16 cases, before a rise associated with unsupervised cases. This indicates a continuing reduction in operating time with supervised training. With the experienced laparoscopic gynaecological surgeon, the plateau was seen after about 10 procedures. We recommend any trainee or gynaecologist to use this information as a guide to the number of supervised procedures required in order to minimize complications and ensure adequate learning.
The diagnostic accuracy of outpatient miniature hysteroscopy in predicting premalignant and malignant endometrial lesions
Authors: Bakour Shagaf H. , Dwarakanath Linga S. , Khan Khalid S. , Newton John R.
Published: March 2003

Objective

To determine the accuracy of outpatient miniature hysteroscopy in the diagnosis of premalignant and malignant endometrial lesions.

Design

A prospective cohort study (1996–1997).

Setting

Minimal access surgical training centre in a large teaching hospital.

Methods

Outpatient hysteroscopy and endometrial sampling was carried out on 248 patients with abnormal uterine bleeding. Any patients unable to undergo these outpatient procedures were admitted for a formal inpatient hysteroscopy and curettage. Test performance characteristics were computed for hysteroscopy, comparing its findings with the histological diagnosis which served as a ‘gold standard’.

Main outcome measures

The estimate of the accuracy of the hysteroscopic findings was based, for binary results, on sensitivity, specificity and predictive values. For multilevel results, the diagnostic accuracy was computed using likelihood ratios (LRs). With a normal hysteroscopy result, an LR of <1 indicated a decreased probability that a premalignant/malignant lesion was present, whereas with an abnormal hysteroscopy result, an LR of >1 indicated an increased probability that such a lesion was present.

Results

Hysteroscopy revealed features of normal endometrium in 228 women, of whom 12 were found histologically to have premalignant hyperplasia/cancer. Hysteroscopic features of premalignant/malignant endometrial lesions were suspected in 20 patients but the diagnosis was confirmed histologically in six cases only. This amounted to a sensitivity of 33.3% (95% confidence intervals (CI) 14.4–58.8), a specificity of 93.9% (95% CI 89.8–96.5), a positive predictive value of 30.3%. (95% CI 12.8–54.3), and a negative predictive value of 94.7%. (95%CI 90.8–97.1). Analysis using likelihood ratios revealed that for a normal hysteroscopy the LR was 0.7 (95% CI 0.5–0.9). The LR was 1.9 (95% CI 0.5–6.6) when there was intermediate abnormality (increased endometrial thickness, abnormal vascularization, polypoid formations, mamillations and cerebroid irregularities). The LR was 51.1 (95% CI 7.9–326.9) when there was definite hysteroscopic abnormality (intermediate abnormality features associated with irregular polylobular friable excrescences with necrosis or bleeding).

Conclusion

The probability of the presence of a premalignant/malignant lesion is not particularly altered by the finding of normal hysteroscopic appearances or of intermediately abnormal features. However, if the hysteroscopic findings are definitely abnormal, the probability of there being a premalignant/malignant lesion is substantially increased. Normal findings at hysteroscopy are not conclusive and do not eliminate the need for endometrial sampling as they are not a substitute for benign findings on histological investigation.
How much gas is required for initial insufflation at laparoscopy?
Authors: Phillips Graham , Garry Ray , Kumar Chandra , Reich Harry
Published: March 2003

Objective

To determine how much gas is required for initial insufflation of the abdomen at laparoscopy.

Design

A prospective observational study.

Setting

Specialized minimal access gynaecological operating theatre in a district general hospital.

Subjects

43 female patients undergoing laparoscopy.

Interventions

In 30 patients, changes in the vertical depth of the pneumoperitoneum at the umbilicus were measured when the volume and pressure of the insufflated CO2 was changed. The depth was also measured in response to changes in the downward force applied to the umbilicus with insertion of the primary cannula. Non‐invasive monitoring of respiratory and circulatory parameters was carried out on a further 13 patients during these procedures and with variation in head‐down tilt.

Main outcome measures

The vertical depth of the pneumoperitoneum, and cardiovascular and respiratory parameters.

Results

When a downward force of 3 kg force is applied at the umbilicus, the mean vertical depth of the pneumoperitoneum is only 0.6 cm (the range includes zero) when the intra‐abdominal pressure is 10 mmHg (approximately equivalent to insufflation of 3 l CO2). This increases to 5.6 cm (range 4–8) when the intra‐abdominal pressure is raised to 25 mmHg. The mean volume of CO2 required to achieve a pressure of 25 mmHg is 5.58 l (range 3.7–11.1). The maximum respiratory effects of the 25‐mmHg intra‐abdominal pressure (with the patient flat) are no greater than the effect of the Trendelenburg position with an intra‐abdominal pressure of 15 mmHg. No adverse circulatory effects are demonstrated.

Conclusions

This 25‐mmHg pressure‐limited method produces a greater splinting of the abdominal wall and a deeper gas bubble than the traditional volume‐limited pneumoperitoneum of 2–3 l, which should lead to a reduced risk of injury.
Total laparoscopic tube hysterectomy: a safer option?
Authors: O'Shea Robert T. , Gordon Simon J. , Seman Elvis I. , Verco Christopher J.
Published: March 2003

Objective 

To compare outcomes in women undergoing total laparoscopic hysterectomy performed with the assistance of a colpotomizing tube (TLTH), with those in women in whom a laparoscopically assisted hysterectomy (LAH) procedure was performed.

Design 

A retrospective review of consecutive patients.

Setting 

State health service patients were treated at Flinders Medical Centre, Adelaide, South Australia, and private patients were treated by the same surgeons in three private hospitals in metropolitan Adelaide.

Subjects 

A total of 227 women who underwent operation between January 1996 and August 1999.

Interventions 

The women involved in the first two years of this study exclusively underwent an LAH, whilst those in the latter 18 months underwent a TLTH.

Main outcome measures 

These included intraoperative complications, including significant haemorrhage, ureteric, bladder, vascular and bowel injury; postoperative complication rates for vault infection, late bowel and ureteric injury, and miscellaneous febrile morbidity. Also documented were the operating time, nonautologous blood transfusion, operation–discharge interval, and readmission with a complication.

Results 

The women having the TLTH procedure had significantly fewer intraoperative complications (χ2 = 8.07, P = 0.004) in comparison with the LAH group; postoperative complications were not statistically different. The mean operating times and readmission rates with surgical complications were equivalent for the two groups. The hospital stay was shorter by 1.5 days for the women having a TLTH (t = 8.39, P < 0.001), and the estimated blood loss was less than half of that for the LAH patients (t = 8.94, P < 0.001); nonautologous blood transfusion was not needed in either group.

Conclusion 

Total laparoscopic hysterectomy utilizing the nondisposable colpotomizing tube and uterine manipulator has both fewer intraoperative complications and reduced blood loss when compared with laparovaginal hysterectomy, and is a safe alternative to LAH.
Endometriosis of liver and diaphragm: is the diagnosis often missed?
Authors: Bhaumik J. , Hefni M.A.
Published: March 2003

Objective To report three cases of endometriosis of the liver, in two of which there was also pleural endometriosis.

Subjects Three patients who underwent diagnostic laparoscopy for pelvic pain, two of whom also had pulmonary symptoms.

Conclusion A 360‐degree view at laparoscopy is essential in all patients undergoing diagnostic laparoscopy, even though they may be complaining only of pelvic symptoms.
Urinary incontinence after laparoscopic cervical sacropexy for severe uterine prolapse
Authors: Liang Ching‐Chung , Chang Shuenn‐Dhy , Lo Tsia‐Shu
Published: March 2003

Objective To describe successful management of postoperative urinary incontinence in a woman who underwent laparoscopic cervical sacropexy for severe genitourinary prolapse.

Setting Tertiary medical center.

Subject A 40‐year‐old woman, who suffered from severe uterine prolapse and wished to have her uterus preserved, underwent laparoscopic cervical sacropexy. She began to suffer from stress urinary incontinence at 3 months after surgery.

Results The patient underwent a minimally invasive tension‐free vaginal taping using procedure, which allowed her to regain a normal social life.

Conclusions The patient's severe uterine prolapse was repaired by means of laparoscopic cervical sacropexy, and she benefited from relatively less postoperative pain and quicker recovery. Although stress urinary incontinence developed 3 months after surgery, the patient regained continence after minimally invasive tension‐free vaginal taping.
Excision of a haeophilic pseudotumour of the ilium, complicated by fistulation
Authors: Heeg  , Smit  , Meer J. Van Der , Horn J. R. Van
Published: March 2003

We report the case of a patient with a haeophilic pseudotumour of the ilium who developed chronic fistulation, 6 months after en‐bloc resection. During the initial resection, the large defect in the iliac wing was filled with bone cement, which may have contributed to fistula formation. A second surgical procedure consisted of excision of the fistula and bone cement and the dead space was obliterated by bringing the gluteus medius muscle into the defect. The fistula recurred, however. Re‐excision of the fistula and obliteration of the dead space by a pedicled rectus abdominis muscle flap resulted in eradication of the fistula. We emphasize the importance of obliteration of dead space, resulting from large pseudotumour resection. The use of bone cement is not advocated. If a fistula does occur, a pedicled rectus abdominis muscle flap may be considered.
Evaluation of recombinant von Willebrand factor in a canine model of von Willebrand disease
Authors: Schwarz  , Dorner  , Mitterer  , Mundt  , Schlokat  , Pichler  , Turecek
Published: March 2003

Dutch Kooiker dogs with hereditary von Willebrand disease have undetectable levels of von Willebrand factor (vWF), resulting in spontaneous haemorrhage of mucosal surfaces similar to the clinical picture of von Willebrand disease in humans. We used this canine model of von Willebrand disease to study the in vivo effects of a new recombinant von Willebrand factor (rvWF) preparation that contained all species of vWF multimers compared with a rvWF fraction containing only low molecular weight multimers (LMW‐rvWF) and with a plasma‐derived factor VIII/vWF concentrate (pdvWF). Administration of rvWF in these vWF‐deficient dogs resulted in a vWF:Ag half‐life of 21.6 h in one dog and 22.1 h in a second dog. Administration of pdvWF resulted in a half‐life for vWF:Ag of 7.7 h, and LMW‐rvWF, 9 h. The in vivo recovery of vWF:Ag after administration of rvWF was 59%, 64% and 70% in three dogs, respectively; 33% after pdvWF, and 92% after LMW‐rvWF. The in vivo recovery of ristocetin cofactor (RCoF) was 78%, 110% and 120% for rvWF, and 25% for pdvWF. Both rvWF and pdvWF caused increases in FVIII. Although no effect was seen on bleeding time at the dosages used, the rate of blood flow from cuticle wounds was reduced after a single bolus administration of rvWF. The rvWF was able to control a severe nose bleed in one dog.
The use of the Port‐A‐Cath in children with haemophilia — a review
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , VAN DEN BERG H. M. , FISCHER K. , ROOSENDAAL G. , MAUSER‐BUNSCHOTEN E. P.
Published: March 2003

Summary. Port‐A‐Caths have been used increasingly in children with severe haemophilia. In non‐inhibitor patients where Port‐a‐Caths were used to facilitate long‐term prophylaxis, the infection rate is rather low and ranges in the various studies from 0 to 29%, with a median follow‐up time of about 27 months. Patients that received the Port‐A‐Cath for the induction of immune tolerance (inhibitor patients) have a high infection rate of 50% to 83%. Although this percentage is high, good venous access is extremely important, especially in this group. The number of both inhibitor and non‐inhibitor patients in the studies are very small, and a prospective survey is important to obtain more adequate data.
Factor concentrates for haemophilia in the developing world
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , BIRD A. , ISARANGKURA P. , ALMAGRO D. , GONZAGA A. , SRIVASTAVA A.
Published: March 2003

Summary. The success in the management of haemophilia in the last two decades has been predominantly due to the availability of sufficient quantities of safe factor concentrates. Unfortunately, the prohibitive cost of these products has prevented this benefit from being available to the vast majority (∼80%) of haemophiliacs living in the developing world. A few developing countries have established facilities for the production of low‐ to intermediate‐purity factor concentrates locally. The infrastructure required to achieve this can be very basic. The experience in South Africa, Thailand, Cuba and Brazil, described herein, shows that this approach provides factor concentrates which are very economical in comparison with more purified commercial products. This has had a major impact on the quality of haemophilia care in these countries. Wide availability of low‐cost factor concentrates has made these products accessible to a large number of haemophiliacs and even made home therapy possible. The effort to provide these products results in improvement of the blood transfusion services. This, in turn, contributes to better facilities for patients with other transfusion‐dependent diseases and society in general. Installation of small plasma fractionation plants is also a viable option. This not only allows processing of large pools of plasma for greater quantities of factor concentrates but also provides albumin and immunoglobulin. The revenue generated from the sale of the other products has been used to improve and subsidize haemophilia care. It is concluded that local production of intermediate purity factor concentrates in developing countries is absolutely necessary. A well organized transfusion service is required to collect adequate quantities of plasma for fractionation.
Proprioceptive training in haemophilia
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , BUZZARD B. M.
Published: March 2003

Summary. Joint and muscle injury associated with direct damage to the tissues and muscle atrophy may ensue following immobility. Rehabilitation of the injury is linked with the return to normal functional values such as range of motion, muscle strength, and muscle tone. It is, however, likely that subtle changes or differences still exist in the site of injury or haemarthrosis. In particular proprioception may be distorted due to the direct injury of sensory receptors and to feedback systems. The implications of such damage are important, where proprioception plays an important part in the control, timing and organisation of coordinated bodily actions.
The genetic basis of inhibitor development in haemophilia A
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , TUDDENHAM E. G. D. , MCVEY J. H.
Published: March 2003

Summary. Inhibitor development is now the main complication of replacement therapy in haemophilia A. Given that most severely affected patients make no detectable factor VIII, it is perhaps surprising that only ˜30% actually mount an immune response to factor VIII as a foreign antigen. Those that do mostly have major factor VIII gene lesions. The association of HLA genotype with inhibitors in patients with identical mutations is weak. Environmental factors may be more important than genetic in antibody response to factor VIII.
Discrepancies in potency assessment of recombinant FVIII concentrates
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , BARROWCLIFFE T. W. , RAUT S. , HUBBARD A. R.
Published: March 2003

Summary. Results of assays of recombinant FVIII concentrates have been reviewed over a 10‐year period. Initially there was wide variability between laboratories but this was minimised by the development of standardised assay methodology, in particular the use of haemophilic plasma for pre‐dilution and 1% albumin in assay buffers. Using this standardised methodology and concentrate standards, there were no major diferences in potency between one‐stage, two‐stage, and chromogenic assays on the two full‐length recombinant FVIII concentrates. However, using a plasma standard, the chromogenic method gave much higher potencies than the one‐stage method on the same concentrates, and this explains a similar discrepancy found in patients' post‐infusion samples after injection of recombinant concentrates. It is suggested that concentrate standards be used for such post‐infusion samples in order to minimise this discrepancy.
Females with von Willebrand disease: 72 years as the silent majority
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , KOUIDES P. A.
Published: March 2003

Summary. The monthly challenge of menstruation as well as the haemostatic challenge of childbirth post partum renders more females than males symptomatic with von Willebrand disease. Among vWD patients, the obstetrical and gynaecological morbidity is certainly more pronounced in Type 2,3 patients compared to Type 1 patients, but even in the latter group there is a high proportion of menorrhagia with associated anaemia, loss of time from work/school and the use of hysterectomy for ultimate control of bleeding. Despite the well known adage of the “gestational palliation” of vWD, there is a high proportion of postpartum haemorrhage in Type 1 patients also especially after the first 24 h after delivery. This may occur despite normalization of the factor VIIIc level in the third trimester, particularly in Type 2,3 patients. With the increasing availability of intranasal/subcutaneous DDAVP that could be readily administered at home for menorrhagia, there recently has been ongoing efforts internationally to determine the prevalence of vWD in females presenting with menorrhagia with a prevalence of 17% combined from two studies of 180 patients total. Issues remain regarding the optimal dose/schedule of intranasal/subcutaneous DDAVP for menorrhagia and the relative efficacy of antifibrinolytic agents. The proper role of oral contraceptives and danazol also deserves further study in vWd patients with menorrhagia. In sum, a comprehensive care approach in females with vWD is warranted analogous to the successful model of care of male haemophiliacs with the intent to (a) reduce unnecessary surgical interventions for menorrhagia, (b) improve the quality of life during menses and (c) optimize peri‐partum management.
The emerging needs of persons living with haemophilia and HIV/AIDS in British Columbia
Authors: TAYLOR
Published: March 2003

The Haemophilia Programme Enhancement Project (HPEP) was initiated in 1991 to assist Haemophilia Programme staff meet the increasing and complex needs of persons living with haemophilia and HIV/AIDS. A review of the HPEP in 1997 revealed that the needs of this population have changed due to the advances in medical treatment, laboratory monitoring and the proliferation of HIV/AIDS expertise and resources. Continued roles for the HPEP include triage and liaison with HIV specialists to ensure appropriate care, given the possible haematological complications that coexist with HIV and/or liver disease. Access to resources remains problematic for those living in remote regions of British Columbia, and a strong advocacy presence is needed. Services to␣families and children of persons with HIV and haemophilia is required, especially around disclosure and␣preparation for the stresses incurred during hospitalization.

The fact that many long‐term survivors are living in relatively good health has sparked renewed optimism amongst this group. Those who continue to do well are in the process of re‐evaluating their lives and may need assistance in establishing both short‐ and long‐term goals. Interventions to sustain hope could include individual and family counselling, facilitated support meetings and a commitment to the provision of vocational rehabilitation counselling, re‐training and job placement. For the first time in years, many persons living with haemophilia and HIV are facing an opportunity to look forward into the future and devise ventures which will enhance their feelings of productivity.
Intron 22 inversions in the Turkish haemophilia A patients: prevalence and haplotype analysis
Authors: EL‐Maarri Osman , Kavakli Kaan , Çağlayan S. Hande
Published: March 2003

In about half of the severe haemophilia A cases, the disease is caused by an inversion that split the F.VIII gene into two parts separated by ≈ 300–400 kb. Herein, we show that in the Turkish population this inversion mutation accounts for 29% of 141 haemophilia A cases and 42% of severe cases. Most of the inversions are of the distal type (72%) whereas nine were of the proximal type (28%). Haplotype analysis using 4 markers in the F.VIII gene did not reveal a single haplotype associated with the inversion. However, the pre‐ valence of one haplotype: HindIII (–) – Int13 (CA)20– Int22 (CA + CT)26–XbaI (–) is higher in the inversion patients. Since founder effect is excluded for the inversion patients, our results suggest that some as yet unknown factor(s) may make these alleles more prone for the inversion. However, a bias due to the low number of studied cases cannot be excluded.
Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia
Authors: Nelson  , Maeder  , Usner  , Mitchell  , Fenstermacher  , Wilson  , Gomperts  ,   THE HEMOPHILIA GROWTH DEVELOPMENT STUDY
Published: March 2003

The prevalence of intracranial haemorrhage (ICH) in our population of haemophiliacs was 12%. The incidence of ICH was ≈ 2% per year. At entry, 7% (21/309) had clinical histories of ICH without MRI evidence of old haemorrhage, indicating that either the haemorrhages had completely resolved, that routine MRI sequences are not particularly sensitive for the detection of old blood products, or a combination of both of these factors. One half (4/8) of the ICHs documented by entry MRI were clinically silent, and three of the 11 incident cases documented by MRI were clinically silent. HIV infection did not increase the risk of ICH.
Financial aspects of haemophilia care in Puerto Rico and other Latin American countries
Authors: Santiago‐Borrero  , Ortiz  , Rivera‐Caragol  , Maldonado
Published: March 2003

The present cost of optimal care in haemophilia is very high. The paradigm of comprehensive care approach, including the essential elements of continuous integrated multidisciplinary health services and the provision of home care with early use of antihaemophilic products requires abundant economic resources that usually are not readily available in nonaffluent countries. A cost‐effective comprehensive paediatric haemophilia programme has been operating in Puerto Rico during the last 15 years that provides quality care to over 90% of paediatric haemophiliacs, and is financed mainly by the local government health system. Efforts are also being made to provide and/or coordinate health care to all adult haemophilic patients through the Puerto Rico Pediatric Hemophilia Treatment Center.

Information on the haemophilia care available in Latin American countries is scanty. The data available indicate that with a few exceptions, haemophilia care in this vast region is suboptimal. Apparently, early diagnosis is not common, there is lack of accessibility of services in most countries, comprehensive care is not the rule, safe high‐purity AHF concentrates are used infrequently, and home care is used rarely. The main antihaemophilic products used are fresh frozen plasma and cryoprecipitate due to the high cost of modern antihaemophilic factor concentrates. The average per capita income of the main Latin American countries is about one‐quarter of that of the USA and Canada. The existing economic situation of most Latin American countries would make it very difficult for them to purchase modern antihaemophilic products regularly and provide quality comprehensive care to their haemophilia patients, unless they make special efforts and get some type of external help. As a result of this study recommendations are made to improve the quality and accessibility of services to haemophilia patients in Latin America and other nonaffluent countries.
The role of orthoses in the management of elbow joints in persons with haemophilia
Authors: Heim M. , Wershavski M. , Martinowitz U. , Varon D. , Checick A. , Azaeia M.
Published: March 2003

The elbow joint is extremely prone to haemarthroses, and when these occur the elbow requires support and rest. Supporting the limb with a simple collar‐and‐cuff sling, a triangular bandage either with or without a shoulder immobilization device will provide an analgesic effect without adding an unnecessary heavy orthosis. As the swelling subsides and the pain lessens a dynamic orthosis aids in the support and compression. When considering functional bracing of the elbow joints there are a number of basic principles to be followed. One requires to consider problems of orthosis suspension, two dimensional motion and stabilization in the functional range of motion. This article provides the rationale for the special needs of persons with haemophilia who suffer from involvement of their elbow joints.
Acquired Haemophilia – a study of ten cases
Authors: Saxena  , Mishra  , Kashyap  , Choudhry  , Mahapatra  , Bhargava
Published: March 2003

Clinico‐haematological features in 10 patients with acquired Haemophilia are presented. Three patients had FVIII inhibitors following pregnancy while in six the cause for development of inhibitors could not be determined. One patient had acquired von Willebrand’s disease. Lupus anticoagulant coexisted with Factor VIII inhibitors in three patients. All patients presented with sudden onset of bleeding without any past or family history of a bleeding disorder. Factor VIII inhibitor levels ranged from 8 to 512 Bethesda units in the nine patients. Immunosuppressive therapy was given to 8 patients, consisting of CVP regimen or corticosteroids with endoxan or cyclosporin. Seven patients had clinical and laboratory responses and one patient did not respond. One patient had severe postpartum bleeding with acute shock which was controlled with FEIBA. Diagnosis and management of idiopathic acquired Haemophilia, thus, continues to be a major challenge, and among acquired Haemophilia, postpartum Haemophilia has good prognosis.
Orthopaedic outcome of total knee replacement in Haemophilia A
Authors: Cohen  , Heim  , Martinowitz  , Chechick
Published: March 2003

A consecutive series of 16 patients with classical Haemophilia underwent 21 total knee replacements between 1989 and 1997 for haemophilic arthropathy. The patients received Factor VIII replacement therapy via continuous infusion, and fibrin glue was used to facilitate haemostasis. Three different types of prostheses were used. A follow‐up evaluation was undertaken between 2 and 10 years after the operation (mean 5.6 years) and two patients with infection were excluded. Knee scores averaged 77.5 (pre‐operative 24.1) and functional scores averaged 84.4 (preoperative 23.2). There were no cases with aseptic loosening of the prosthesis. Complications included one early deep infection controlled by conversion of the TKR into an arthrodesis, one case of late septic loosening that had to be re‐operated upon, one case of patellar dislocation, two cases of stiff knee (fibro‐arthrosis) that required manipulation under anaesthesia, one postoperative hepatitis, one superficial infection treated by incision and drainage and four febrile patients with no clear source of infection, who responded to antibiotics alone. In conclusion, TKR offers haemophilic patients a long‐lasting improvement of their quality of life and we therefore advocate its use with the appropriate indications.
Management of factor XI inhibitor for cardiac intervention: successful treatment with immunosuppressive therapy and plasma exchange
Authors: Teruya J. , Styler M.
Published: March 2003

Two cases with congenital homozygous factor XI deficiency developed a factor XI inhibitor following repeated plasma transfusions. Case 1 was given cyclophosphamide, intravenous immunoglobulin, and steroids. The factor XI inhibitor disappeared on day 103 and cardiac catheterization was performed without complications after giving fresh frozen plasma. Case 2 was effectively managed by plasma exchange for cardiac catheterization and surgery. However, after five plasma exchange procedures, the same plasma volume exchange was not effective in shortening the activated partial thromboplastin time (APTT). A significant heparin rebound occurred 4 h after heparin neutralization with protamine sulphate for which the patient needed to have a blood clot evacuated from around the heart.
Emotional and behavioural problems and family functioning in children with haemophilia: a cross‐sectional survey
Authors: Evans M. , Cottrell D. , Shiach C.
Published: March 2003

A comparative study is presented about emotional and behavioural problems in haemophilia and family functioning. This cross‐sectional survey looked at boys, aged between 4 and 15 years, with haemophilia and compared them with a group of their healthy school peers. A basic demographic questionnaire was used for both groups along with the Child Behaviour Checklist (CBCL) and the Family Assessment Measure (FAM). Seventeen of 24 families of boys with haemophilia participated (70.8% response). The comparison group consisted of 12 boys, i.e. 70.6% of the haemophilia sample. The groups did not differ in terms of the children’s ages and family sizes but significantly fewer of the mothers of the boys with haemophilia worked outside the home. The two groups were compared for scores on the CBCL and FAM. More problems were identified in the haemophilia group on both measures, i.e. there were more emotional, behavioural and family difficulties compared with the healthy group; however, because of the small sample sizes, the differences between the groups did not reach statistical significance. A larger study would be indicated in order to explore these differences further.
Immune tolerance in a haemophilia A patient with high inhibitor using locally prepared lyophilized cryoprecipitate
Authors: Chuansumrit  , Pakakasama  , Kuhathong  , Chantanakajornfung  , Hathirat
Published: March 2003

The immune tolerance in a 12‐year‐old haemophilia A patient was carried out at the Faculty of Medicine, Ramathibodi Hospital, Bangkok in 1998. His inhibitor titres ranged from 10 to 3450 Bethedsa units (BU). He suffered from serious bleeding episodes requiring prolonged hospitalization and the disarticulation of the left knee joint. After obtaining informed consent, locally prepared lyophilized cryoprecipitate (LC), heat treated at 60 °C for 25 h, was given in a dose of 13 units kg−1 body weight of factor VIII three times per week. His inhibitor was increased from 15 to 580 BU within the first 4 weeks of immune tolerance. Finally, it was decreased to 40 BU in the 36th week. The only adverse effect was seroconversion of anti‐hepatitis C virus after receiving 108 bottles of LC for 36 weeks. In conclusion, the locally prepared LC was able to control the bleeding episodes in a haemophilia A patient with high inhibitor. To our knowledge, this is the first reported case in Thailand.
Combined factor V and VIII deficiency in Indian population
Authors: Shetty  , Madkaikar  , Nair  , Pawar  , Baindur  , Pathare  , Ghosh  , Mohanty
Published: March 2003

The clinical and haematological heterogeneity in cases of the rare combined factor V and VIII deficiency has not been reported so far from India. Nine such cases belonging to five unrelated families have been analysed in the present study for the various haematological and clinical parameters. A very mild clinical presentation is seen in all these cases. The clinical manifestations, however, do not correlate with the plasma levels of these factors.
Proposal of a standard approach to dental extraction in haemophilia patients. A case‐control study with good results
Authors: Zanon  , Martinelli  , Bacci  , Zerbinati  , Girolami
Published: March 2003

We found no case–control studies on dental extraction in haemophilia patients in the literature even though the use of antifibrinolytic agents following a single infusion of factor VIII or IX has been accompanied by a lower number of bleeding complications in dental extractions. In this study we verified the incidence of bleeding complications after dental extraction in a group of 77 haemophilia patients. One hundred and eighty‐four male patients requiring dental extraction represented the control group. All haemophilia patients received 20 mg kg–1 of tranexamic acid and a single infusion of factor VIII or IX to achieve a peak level about 30% of factor VIII or IX in vivo prior to dental extraction. Forty‐five of 98 (45.9%) dental extractions in haemophilia patients and 110 of 239 (46%) dental extractions in the control group were surgical ones. We registered two bleeding complications in the group of haemophilia patients (one late bleeding and one haematoma in the site of the anaesthetic injection) and one (a late bleeding) in the control group. The difference of bleeding complications in the two groups of patients were not statistically significant (P=0.2; OR 0.2; CI 0.01–2.22). The protocol proposed in this study, characterized by the feasibility and the number of haemorrhagic complications not different from normal population, make dental extractions in haemophilia patients possible on an out‐patient basis with a cost reduction for the community and minor discomfort for the patients.
Factor VIII gene polymorphisms in the Asian Indian population
Authors: Chowdhury M. R. , Herrmann F. H. , Schroder W. , Lambert C. T. , Lalloz M. R. A. , Layton M. , Kumbnani H. K. , Kabra M. , Menon P. S. N. , Verma I. C.
Published: March 2003

Little is known about the heterozygous frequency of factor VIII gene markers in the Asian Indian population. The objective of this study was to establish the heterozygous frequency of polymorphic markers within and flanking the factor VIII gene in Indians and identify those most informative for carrier screening and prenatal diagnosis.

Factor VIII gene polymorphism analysis at intragenic and extragenic sites was carried out by the polymerase chain reaction (PCR) method and Southern blot procedure. Sixty‐three Asian Indian haemophiliacs and their families were screened. A control group of 150 women from nonhaemophilic families were screened for two markers, HindIII and BclI.

Among the intragenic markers studied, the HindIII restriction fragment length polymorphism (RFLP) showed the highest heterozygous frequency (0.52) followed by the intron 13 (0.47) and intron 22 (0.44) short tandem repeats (STRs). Among extragenic markers, TaqI had the highest heterozygous frequency (0.75) followed by BglII (0.54). The intron 22 inversion mutation was observed in eight (40%) of 20 severe cases.

In the population studied the most diagnostic polymorphisms were the intragenic markers, intron 22 (70%) STR followed by the intron 13 (52%) STR and HindIII (52%) RFLP, and the TaqI (50%) extragenic marker. Application of HindIII, BclI and the intron 22 dinucleotide repeat combined were diagnostic in 87.2% of haemophilia A families studied.
Current therapy for rare factor deficiencies
Authors: Di Paola J. , Nugent D. , Young G.
Published: March 2003

Haemophilia A and B and von Willebrand disease account for 80–85% of all inherited bleeding disorders. The other 15% are represented by deficiencies of fibrinogen, prothrombin, or factors V, VII, X, XI, or XIII. In addition, acquired factor deficiencies are seen in a variety of conditions ranging from malignancies to autoimmune disorders. The spectrum of symptoms in these conditions varies from severe and life‐threatening haemorrhage to a mild bleeding diathesis. The diagnosis depends on demonstration of decreased activity of one of the clotting factors. Due to the rarity of each of the individual factor deficiencies, purified factor concentrates are not as readily available as they are for haemophilia A and B. Treatment of rare clotting factor deficiencies consists of the most purified blood product available that contains the missing factor. Depending on which factor is deficient, either purified concentrates, prothrombin complex concentrates, cryoprecipitate, or fresh frozen plasma can be used. In addition, recombinant factor VIIa is available for treating factor VII deficient patients.
The technique of synoviorthesis
Authors: Rodriguez‐Merchan E.C. , Goddard N.J.
Published: March 2003

Synoviorthesis (medical synovectomy) is a commonly utilized procedure employed in the management of recurrent intra‐articular bleeds and secondary chronic synovitis in haemophilic patients. The procedure involves the intra‐articular administration of an agent in order to induce fibrosis in the inflamed synovium so reducing the bleeding tendency. Such agents may either be chemical based (osmic acid, rifampicin) or radioactive (yttrium, gold or phosphorus). Whichever agent is employed care must be taken to avoid extra‐articular complications (radiation burn and/or inflammatory reaction) as a result of extravasation or needle track contamination. The most frequently affected joints in haemophilia are the elbows, knees and the ankles, and to a lesser extent the shoulders and hips. This article outlines the techniques of injection of the five aforementioned joints, with details of the anatomical landmarks to perform the injections correctly. Injection of the elbows, knees and ankles may be carried out simply on an out‐patient basis under local anaesthesia. However, it is advisable to perform injection of the shoulder or hip under radiographic control in order to ensure accurate placement. Very young children may require either sedation or a general anaesthetic. Strict asepsis is naturally a paramount requirement.
A haemophilia A and B molecular genetic diagnostic programme in Hungary: a highly informative and cost‐effective strategy
Authors: Klein I. , Andrikovics H. , Bors A. , Nemes L. , Tordai A. , Váradi A.
Published: March 2003

Our aim was to set up a protocol in order to provide carrier and prenatal diagnosis to Hungarian haemophilia A (HA) and B (HB) patients and their relatives. For HA, a combination of direct mutation detection and some indirect marker analyses were used: the detection of the inversion mutation and analysis of three polymorphisms, BclI, IVS13 (CA)n and P39(CA)n. In severe cases, direct mutation detection was performed first. In inversion‐negative severe cases and in moderate and mild cases, indirect methods were used. For carrier and prenatal diagnosis in HB, four polymorphisms, DdeI, TaqI, XmnI, and HhaI were examined. Our DNA bank contains samples from 50 HA families (34 severe, 15 moderate and one mild) and seven HB families from different parts of the country. In 100% of the HA cases either the gene inversion and/or at least one of the polymorphisms was found to be informative for carrier or prenatal diagnosis. In the HB cases, an informative marker was found in 95% of the cases (19 of 20). We conclude that these strategies are sufficient to make genetic diagnosis available to almost all HA and HB families in the region. This approach is highly informative and cost‐effective, so it can be very useful in countries where direct sequencing of genes for factor VIII and IX is not available for routine diagnosis.
Vitronectin in clotting factor IX concentrates
Authors: Josic D. , Kannicht C. , Löster K. , Pock K. , Iberer G. , Buchacher A.
Published: March 2003

Highly purified, plasma‐derived factor IX (FIX) concentrates are produced in large part by a combination of anion exchange and heparin affinity chromatography. However, the concentrates still contain some accompanying proteins. The main impurity has turned out to be the adhesive glycoprotein, vitronectin. It occurs in concentrates exclusively in its multimeric form, in contrast to the situation in plasma. The multimeric vitronectin can be removed either by nanofiltration with a crossflow system or by size‐exclusion chromatography. When these FIX concentrates are used as therapeutic agents, the fact has to be taken into account that considerable amounts of multimeric vitronectin are given to the patient. The physiological consequences of the dosage of this protein have not yet been investigated. Although no thrombogenicity has been reported in connection with the above‐mentioned FIX concentrates, we recommend that the impurity should be removed from the preparation with the methods described here.
Development of inhibitors in patients with haemophilia from India
Authors: Ghosh K. , Shetty S. , Kulkarni B. , Nair S. , Pawar A. , Khare A. , Baindur S. , Mohanty D.
Published: March 2003

Four hundred and seven patients (352 haemophilia A and 55 haemophilia B) were investigated for the presence of factor VIII and IX inhibitors. Twenty‐four out of 292 severe and two out of 36 moderate haemophilia A patients showed the presence of inhibitors. The mean age at development of inhibitors was 17.7 years (range 6–52 years). In 12 patients the inhibitors were detected due to suboptimal response to factor replacement therapy (symptomatic) and in the remaining 14 patients the inhibitors were detected during the routine screening of the patients’ samples for inhibitors. They had, however, responded well to the usual doses of factor concentrates and there was no suspicion in these patients that they had developed an inhibitor (asymptomatic). There were two families in which the inhibitors were detected in more than one family member. The level of inhibitors in symptomatic patients ranged from 2.2 Bethesda units (BU) mL–1 to 460.6 BU mL–1, and in asymptomatic patients it ranged from 0.8 BU mL–1 to 3.2 BU mL–1. The inhibitors persisted in all patients except one, who developed an inhibitor postoperatively for a brief period of 3 months. All these patients were followed up from first factor exposure and were tested for inhibitors at least twice a year. The mean number of exposure days before they developed inhibitors was 47.5 exposure days (range 17–98 exposure days). No inhibitors appeared after more than 100 exposure days in any of the patients. When 50 consecutive patients were investigated for intron 22 inversions of the factor VIII gene, 17 patients were found to be positive for inversions (10 proximal inversion; seven distal inversion) out of whom four patients developed inhibitors, three patients belonging to the same family. Out of 35 haemophilia B patients, only one patient developed an inhibitor. The overall prevalence of inhibitors was thus 8.2%, which is similar to the reports from western countries, prior to the introduction of highly purified factor concentrate therapy.
Postpartum acquired haemophilia: clinical recognition and management
Authors: Kashyap R. , Choudhry V. P. , Mahapatra M. , Chumber S. , Saxena R. , Kaul H. L.
Published: March 2003

Postpartum acquired haemophilia is a rare but serious complication of an otherwise normal pregnancy. Patients usually present with postpartum haemorrhage (PPH) or uncontrolled bleeding following surgical interventions, which fail to respond to conservative treatment. A high index of clinical suspicion along with early laboratory diagnosis and prompt institution of appropriate therapy is essential for the management of acute bleeding episodes. Our patient, a 32‐year‐old female, presented with severe PPH and shock. She had undergone dilation and curettage three times, with subsequent total abdominal hysterectomy and internal iliac artery ligation, before she was diagnosed with acquired haemophilia (factor VIII autoantibodies) and an inhibitor level of 8 Bethesda units (BU). The patient underwent an abdominal laprotomy for removal of the abdominal packing used in the previous operation, and blood and blood clots, and was given FEIBA® therapy. The patient responded to these measure and the factor VIII inhibitor level decreased to 2 BU at the time of discharge 10 weeks later.
Correlation between clinical, radiological and ultrasonographical image of knee joints in children with haemophilia
Authors: Klukowska A. , Czyrny Z. , Laguna P. , Brzewski M. , Serafin‐Krol M. A. , Rokicka‐Milewska R.
Published: March 2003

The aims of the study were to evaluate the clinical, radiological and ultrasonographical images of knee joints in children with severe haemophilia and von Willebrand’s disease, to determine the correlation between these images and to assess the usefulness of ultrasonography (USG) in evaluating the intensity of haemophilic arthropathy. Thirty‐nine boys were included in the study, all of them with a past history of knee bleeds. The average age of the children was 10.02 ± 3.01 years. In patients with slight (1–3 points) and moderate (4–7 points) radiological changes in knee joint bones, an increase in synovial fluid, considerable hypertrophy and inflammation of the synovium were observed in USG. In haemophilic patients with severe (8–13 points) bone changes, the amount of fluid was usually normal and there was slight inflammation but considerable hypertrophy of the synovium. Radiological evaluation of haemophilic arthropathy was made according to the Pettersson classification. A good correlation between the degree of cartilage damage in USG and the progression of bone changes in radiographs was found. Cartilage and bone damage progressed with the increase in the number of intra‐articular haemorrhages into the knee joint. In our opinion USG is useful in evaluating the fluid, synovium and cartilage of joints in haemophiliacs.