The effect of bleeding patterns on the response of haemophilic haemarthroses to different doses of factor VIII

Summary Three hundred and thirty-nine consecutive bleeds into the knees, elbows and ankles of severe haemophiliacs were graded 1 if more than 50% of normal movement was present, and graded 2 if less than 50% of normal movement was present. Nursing staff then administered randomly allocated doses of 7, 14 or 28 units of factor VIII per kg. Medical staff unaware of initial dosage assessed progress thereafter at 12-hourly intervals. Grade 1 bleeds into ‘normal’ joints showed no difference in response to the three dosage regimes, but grade 2 bleeds did worse on low doses. There was no significant difference in the response to each dose of bleeds into restricted and into target joints. However, when a restricted joint became a target joint as well, both grade 1 and grade 2 bleeds did badly on low doses. The percentage of patients with bleeds into these joints whose range of movement had not returned to baseline 48 h after receiving a low dose of factor VIII was significantly higher than those who had received the higher doses.     

A double-blind controlled trial of two dose levels of factor VIII in the treatment of high risk haemarthroses in haemophilia A

One hundred and thirteen haemarthroses involving the knees, ankles and elbows of 29 severe haemophiliacs presenting with at least two of the risk factors, pain, tenderness, loss of more than 50% of movement and a delay of more than 3 h in treatment were studied. Each was given either a 20% or 40% dose of factor VIII and progress was then reviewed by medical staff unaware of the initial dosage. There was no significant effect on the retransfusion rate nor on the time to complete resolution. However, the difference between the percentage of patients showing residual movement restriction was significantly in favour of the high dose at 24, 36 and 48 h when all the bleeds were pooled and at 48 h for elbow bleeds.     

Successful angiographic embolization of recurrent elbow and knee joint bleeds in seven patients with severe haemophilia

Summary.  In haemophilic joints with high-grade arthropathy, bleeds occur that do not respond to replacement therapy of the deficient coagulation factor. The reason may be pathologically reactive angiogenesis in chronic synovitis. Seven patients with severe haemophilia A or haemophilia B experienced recurrent massive bleeds of one elbow joint or knee joint in the absence of trauma. After initial application of factor VIII or IX (fVIII/fIX; 50 IU kg⁻¹ bodyweight), there was only slow and never complete relief of symptoms. Despite intensive secondary prophylaxis maintaining the plasma level of factor concentrate at minimum 50%, new massive bleeds at the same location occurred. Vascular bleeding was suspected. Angiography of the arteries was performed via the femoral artery. Vessels identified as potential bleeding sources were embolized with embolization fluid (ONYX) in eight joints (six elbow and two knee joints). Under low-dose prophylactic treatment (15 IU fVIII or fIX per kg bodyweight for three times per week), no recurrent severe bleed unresponsive to coagulation factor replacement occurred after a mean observation time of 16 months after embolization. The consumption of factor concentrate decreased to one-third of the amount consumed before embolization. In conclusion, angiographic embolization with a non-adhesive liquid embolic agent might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels.     

The use of an activated factor IX complex (Autoplex) in the management of haemarthroses in haemophiliacs with antibodies to factor VIII

A new activated factor IX product (Autoplex) has been used for the treatment of 18 haemarthroses in three haemophiliac patients with antibodies to factor VIII and a history of high anamnestic response to challenge with factor VIII. Results were evaluated by assessing pain, tenderness, range of movement and girth at 8 and 24 hours. A score of 2 was given for improvement at 8 hours and 1 for improvement at 24 hours. The result was expressed as a percentage of the possible score. Nine episodes treated with less than 35 units of Autoplex/kg had a mean score of 52% and nine episodes treated with more than 35 units/kg had a mean score of 73%. When only the more severe group of bleeds was considered, an even more marked dose related response emerged. When the ratio of the percentage fall in the PT to the percentage fall in the KCCT was plotted against the outcome, a significant correlation emerged (r=0.43; P= 0.02).     

Treatment and prevention of acute bleedings in von Willebrand disease – efficacy and safety of Wilate®, a new generation von Willebrand factor/factor VIII concentrate

Summary.  For many patients with von Willebrand disease (VWD), the replacement therapy with von Willebrand factor (VWF)/factor VIII (FVIII) concentrates is the treatment of choice. To evaluate clinical efficacy, safety and tolerability of Wilate^®, an albumin-free VWF/FVIII concentrate with a ratio of the two haemostatic moieties of approximately 1 to 1, a prospective clinical programme has been designed. The dataset on the treatment and prevention of bleedings is derived from 44 patients (20 males and 24 females) of all VWD types. Thousand and ninety five bleeding episodes were treated with an overall efficacy rating of excellent or good in 96%. The median dose per treatment day was 26 IU FVIII:C per kg. Eighty-one per cent of bleeds were stopped within 1 or 2 days. Gastrointestinal (GI) bleeds needed higher doses (mean 44 IU kg⁻¹) and longer treatment (mean 4 days). Efficacy and dosing data from eight children of 12 or less years of age did not differ significantly from the overall study population. Nineteen patients, including six children, were treated prophylactically for more than 3 months (mean 14.8, range 3–46) with a mean prophylactic dose of 27.4 IU kg⁻¹ and a mean frequency of 1.9 infusions per week. A drop of bleeding frequency from a mean of 4.5 to 1.4 bleeds per month was observed. The overall tolerability was very good. Adverse drug reactions were rare and were mild or moderate in their intensity. The large prospective clinical dataset shows that Wilate^® is efficacious and safe in the treatment and prevention of haemorrhages in all VWD types in both adult and paediatric patients.     

Socioeconomic impact of haemophilia care: results of a pilot study

Summary. Fifty consecutive haemophiliacs were entered into a pilot study of socioeconomic impact of haemophilia treatment. The Short Form 36 was used as an instrument for the assessment of quality of life. Direct and indirect costs were analysed. Incremental cost-effectiveness was expressed as additional costs per joint bleed avoided by prophylactic treatment over on-demand treatment. Thirtynine patients (mean age 35.14 years) were substituting factor VIII according to an on-demand and 11 patients according to a modified prophylactic regimen. There were an average of 9.84 joint bleeds per patient across all patients during the 6-month observation period: on-demand group 10.74 bleeds, prophylactic group 6.64 bleeds. This difference was not statistically different. Significant differences between haemophiliac patients and healthy men were seen in the assessment of their limitations of physical activities, limiting pain and general health. The total cost per patient during the 6 months was DM 24 601 in all patients, DM 17 253 in those on an on-demand base and DM 28 245 in the modified prophylactic group. Patients experienced an average 4.71 days off work: on demand 5.81 days, prophylactic regimen 0 days. The total indirect cost per patient was DM 683; therapy cost per patient was DM 25 284; cost per avoided bleed DM 1680 for on-demand therapy and DM 4228 on prophylaxis. The incremental cost-effectiveness, i.e. the additional costs to avoid one additional joint bleed by prophylactic treatment, was DM 2536. In conclusion, patients receiving prophylactic clotting factor therapy require less additional health care resources, mainly due to the reduction in the number of joint bleeds.     

A brief screening tool for knee pain in primary care (KNEST). 2. Results from a survey in the general population aged 50 and over

OBJECTIVE: To use a brief screening tool to identify knee pain (all knee pain, non-chronic and chronic knee pain) and associated health-care use in the general population aged 50 yr and over. METHODS: A cross-sectional survey was mailed to 8995 individuals registered with three general practices in North Staffordshire, UK. The questionnaire included a Knee Pain Screening Tool (KNEST), the Short Form 36 (SF36), demographic questions and, for those who reported knee pain, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The survey achieved a 77% response. The 12-month period prevalence of all knee pain was 46.8% [95% confidence interval (CI) 45.6%, 48.0%]. Figures for non-chronic knee pain (pain of less than 3 months duration) and chronic knee pain (pain of more than 3 months duration) were 21.5% (95% CI 20.5%, 22.5%) and 25.3% (95% CI 24.3%, 26.4%) respectively. An estimated 6% of the older population had non-chronic but severe knee pain or disability. Thirty-three per cent of all knee pain sufferers had consulted their general practitioner (GP) about their symptom in the last year. This included 34% of those with non-chronic but severe knee pain or disability and 56% of those with chronic and severe knee pain or disability. The use of private treatments or services for knee pain was minimal. A third of those with chronic and severe knee pain or disability had not used any services (including GP) in the last year. CONCLUSIONS: The KNEST is a simple tool for the identification of individuals with knee pain and their health-care use. Focusing only on chronic knee pain will underestimate the total need and demand for health-care in knee pain sufferers in the general older population, as non-chronic as well as chronic knee pain has a significant impact on people's lives and on their use of primary health-care. The KNEST, when combined with the WOMAC, identifies population groups who have potentially diverse health-care needs and who might benefit from effective health-care. These data can be used alongside evidence on effective treatments by service planners when considering needs for the care of older adults in primary care.     

Clinical features of early haemarthroses in severely affected adolescent haemophiliacs

Summary. Six hundred and ninety bleeds into the knees, ankles and elbows of severe haemophiliacs presenting for treatment within 3 h of the onset of symptoms have been studied with the aim of providing clinical information for the haemophiliac patient or his parent treating early bleeding episodes at home. Patients were resident at a boarding school and documentation and follow-up to complete resolution was possible. Stiffness was a presenting symptom in 61% of elbow bleeds, 49% of knee bleeds and 18% of ankle bleeds. Pain was a presenting feature in 79% of ankle bleeds, 55% of knee bleeds and 42% of elbow bleeds. Tenderness was a common feature of ankle bleeds (85%), less so in elbows (55%) and knees (69%). Swelling was a very common feature at all sites and the mean increases in girth of the knees, elbows and ankles were 1.42 cm, 0.88 cm, and 0.62 cm, respectively. All the knee and elbow bleeds and 85% of the ankle bleeds had demonstrable restriction of movement. There was a direct relationship between the degree of swelling, extent of movement restriction and time taken for complete restoration of function, the mean of which was 3.6 days for elbows, 2.5 for knees and 1.1 for ankles.     

A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study

The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (-11.4%-15.7%), P=.059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309.     

Current practice in the management of muscle haematomas in patients with severe haemophilia

Summary. Muscle haematomas (MH) represent 10–25% of all bleeds in patients with severe haemophilia. We performed a cross‐sectional survey on current practice in the management of MH with participation from 22 consultants. The respondents reported 492 MH/year, corresponding an average of 25/centre, mostly associated with trauma. Iliopsoas (55%), calf (18%) and thigh (18%) bleeds were scored as most serious. Half of the respondents distinguished between contusion and strains, whereas the majority (68.2%) did not categorize bleedings as intra‐ or intermuscular, although 77.3% routinely used ultrasound. Half of the respondents used a standard protocol for the management of MH. Twenty of 22 (90.9%) respondents offered physiotherapy in the hospital following MH, with no clear consensus on timing and type of treatment. In a theoretical case, for a 70‐kg patient with a soleus triceps haematoma, the average initial dose of factor VIII was 2730 U (range: 1750–4000) twice daily for 3–5 days. In a similar case of a patient with inhibitors, 31.8% reported first‐line and only use of either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (APCC), while 36.4% switched between bypassing agents. Using rFVIIa, the median dose was 100 μg/kg (range: 85–270) and with APCC, the median dose was 70 U kg^?1 (range: 50–100). The majority (68.2%) did not use antifibrinolytics. Resolution of pain (81.8% & 77.3%) was regarded as the key clinical marker of arrest of bleeding as compared with diminished swelling and improved range of motion. The survey outlines limited consensus in the management of MH in patients with haemophilia and highlights potential topics for future studies.     

FEIBA® in treatment of acute bleeding episodes in patients with haemophilia A and factor VIII inhibitors: a retrospective survey in regional haemophilia centre

Summary.  FEIBA^® (factor eight inhibitor by-passing activity) is used to achieve haemostasis in haemophiliacs with inhibitor. The aim of this study was to evaluate efficacy and consumption of the product in treatment of haemorrhages in haemophiliacs with factor VIII inhibitor, and determine factors that can influence the results of treatment. We used data from our haemophilia centre from years 2000–2008. Six haemophiliacs with factor VIII inhibitor were treated on demand with FEIBA^® for 61 bleeding episodes (45 haemarthroses, six muscle bleeds, six other sites bleeds and four multiple sites bleeds). The median cumulative dose of FEIBA^® per bleeding episode was 205 U kg⁻¹. Bleeding was stopped in 96.7% (59 of 61) of events but re-bleeding occurred in 3 events (4.9%) within 48 h after cessation of bleeding. In home treatment (20 of 61) bleeding stopped in 90% (18 of 20) without recurrence and the median consumption per event was reduced to 153 U kg⁻¹. Without the use of home treatment the median consumption was 250 U kg⁻¹ per event and bleeding ceased definitely in 92.7% (38 of 41) of cases. The cumulative dose of FEIBA^® was lower for three episodes with re-bleeding: median 96 U kg⁻¹ but not in the two cases of ineffective treatment: 361 U kg⁻¹. FEIBA^® in management of bleeding episodes completely resolved the haemorrhage in 91.8% of events and in a further 4.9% if treatment was restarted. Using home treatment saved expenditure due to the lower cumulative dose needed for treatment of haemorrhage.     

Profile of coronary artery disease in Indian women: correlation of clinical, non invasive and coronary angiographic findings

Clinical and risk factor profile of 101 consecutive female patients subjected to coronary angiography was analysed. Coronary angiography showed single vessel disease (SVD) in 15.8 per cent, double vessel disease (DVD) in 12.9 per cent, triple vessel disease (TVD) in 39.6 per cent and normal coronary arteries (NC) in 30.7 per cent. Risk factor profile in patients with angiographic coronary artery disease (group II) included hypertension (HT) in 52.9 per cent, diabetes mellitus (DM) in 44.3 per cent, post menopausal state in 84.3 per cent, positive family history in 51.4 per cent, obesity in 58.3 per cent, low density and high density lipoprotein ratio (LDL/HDL) more than 3.0 in 58 per cent and smoking in 4.3 per cent. Risk factors in 31 patients with NC (group I) included HT in 29 per cent, DM in 6.5 per cent, positive family history in 45.2 per cent, obesity in 45.2 per cent, post menopausal state in 48.4 per cent, LDL/HDL ratio more than 3.0 in 30 per cent and smoking in none. The clinical presentation in group II was unstable angina in 64.3 per cent, stable angina pectoris in 24.3 per cent, myocardial infarction in 4.3 per cent and atypical chest pain in 2.8 per cent. In group I half the patients presented with atypical chest pain. The other modes of presentation included unstable angina 25.8 per cent, stable angina pectoris in 16.2 per cent and myocardial infarction in 6.5 per cent. Predictive value of exercise electrocardiography (Ex ECG) or exercise radionuclide studies (Ex RNU) was 61.7 and 68.4 per cent respectively. DM, post-menopausal state and LDL/HDL ratio more than 3 were significant risk factors in women.(ABSTRACT TRUNCATED AT 250 WORDS)     

Orthopaedic evaluation in children with severe haemophilia A or B submitted to primary prophylaxis therapy in a coagulopathy treatment centre

Summary. There is a lack of publications concerning the use of primary prophylaxis in developing countries. The aim of this study was to evaluate the effectiveness of primary prophylaxis therapy in preventing the development of arthropathy in children with severe haemophilia A or B. From January 1999 to April 2009, a prospective study was carried out involving 39 patients with severe haemophilia A or B. These haemophilia A and haemophilia B patients received 20–40 UI kg^?1 of factors VIII and IX, three and two times per week, respectively. The patients were followed up by a multidisciplinary team. The analysis was carried out in 23 patients who had been on prophylaxis therapy for at least 12 months. The orthopaedic evaluation was performed according to the recommendations of the Orthopedic Advisory Committee of the World Federation of Hemophilia, by evaluating pain and bleeding, and by conducting physical examination and radiological assessment (Pettersson’s Joint Score and magnetic resonance): 82.6% of patients who had used the factor regularly did not present any clinical or radiographic changes in the studied joints; 17.4% used the factor irregularly at the beginning of the treatment and of those, most patients presented mild changes in the joints; and 4.3% presented transient knee and ankle pain in spite of regular factor use. The preliminary results of primary prophylaxis confirm its effectiveness in preventing haemophilic arthropathy. Socioeconomic factors did not play a significant role.     

Massive bleeding episodes in patients with acquired haemophilia--case report

We present two cases with a history of acquired haemophilia with massive haemorrhage in the course of the disease. A 74-year-old man presented to the emergency room with an extensive, progressive swelling and haemorrhage in the region of left knee joint, both upper legs and forearms. Laboratory studies revealed the presence of the factor VIII inhibitor in the titer of 115 Bethesda U/mL, low level of factor VIII activity (19.2%) and severe anemia (Hb - 7.0 g%). The patient was treated with FFP transfusions and prednisone with cyclophosphamide to eradicate factor VIII inhibitor. The remission was achieved and lasts for a two years. A 52-year-old woman presented to the emergency room with an extensive subcutaneous haemorrhage in the region of right knee joint and right lower leg. Laboratory studies revealed the presence of the factor VIII inhibitor in the titer of 30 Bethesda U/mL. The factor VIII activity level was only 4%. The patient did not receive the FFP because the severity of the haemorrhage was low. She was treated with steroids. The factor VIII inhibitor disappeared after 2.5 months of therapy.     

Efficacy, safety and tolerability of recombinant factor VIII (REFACTO®) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria

An open-label, multicentre, postmarketing surveillance study conducted in Germany and Austria with recombinant factor VIII (REFACTO) has enrolled 217 patients (mean age 26.3 years) from 38 haemophilia centres during the first 4.8 years. Most patients (188/217; 86.6%) had severe to moderately severe haemophilia A, of whom 153 completed sufficient diary information for the main efficacy analysis. These 153 patients experienced a median of 6.6 (interquartile range 1.4-18.6) bleeding episodes per year. Patients treated with prophylaxis experienced a median of 4.4 (1.1-9.3) bleeds per year, while patients treated on-demand experienced a median of 22.8 (11.3-29.0) bleeds per year. Overall, most physicians (41/43 [95.3%]) were 'very satisfied' or 'satisfied' with the efficacy of REFACTO in the treatment of bleeding episodes. A total of 137 non-serious adverse events have been reported in 52/217 patients (24.0%) to date. In addition, 129 serious adverse events in 87 patients (40%) were reported, including 41 cases of 'less than expected therapeutic effect' (LETE). Of these, 39 LETE cases were reported in one centre; however, patients in this centre experienced considerably fewer bleeding episodes per year than patients outside this centre. Overall, six patients (2.8%) have developed de novo inhibitors, three of which were considered high titre. Four of these patients were at high risk (0-50 exposure days [ED]) of inhibitor formation, one was at intermediate risk (51-100 ED) and one was at low risk (>100 ED). These results emphasize the benefit of postmarketing surveillance and, overall, this study confirms the efficacy, safety and tolerability of REFACTO in the treatment of patients with haemophilia A.     

Efficacy and tolerability of diclofenac dispersible in painful osteoarthrosis

Summary A multicentre, twelve-week, double-blind, randomized trial was conducted to evaluate the efficacy and tolerability of diclofenac dispersible in patients suffering from osteoarthrosis of the knee and/or hip. Symptomatic adult patients (N=129) of either sex were treated with diclofenac dispersible or the conventional enteric-coated tablet of diclofenac sodium 50 mg orally, thrice daily. Both formulations of diclofenac led to comparable and clinically significant reductions in the intensities of pain at rest and during activity within 1 week of therapy initiation. More than 70% of patients in both treatment groups had no or mild pain on full passive movement by the end of the study with the Lequesne Index showing a reduction of around 50% from initial values. Overall assessments of efficacy by the patient and the investigator indicated a positive response rate for both diclofenac formulations ranging between 71% and 82%. The proportion of patients reporting adverse effects, predominantly gastro-intestinal, was slightly higher in the dispersible group, 40.3%, compared to 37.3% with enteric-coated diclofenac sodium.     

Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis

Summary A multicentre randomised, double-blind, parallel group, general practice study was undertaken to investigate the efficacy and safety of aceclofenac (200 patients, 100mg twice daily and placebo once daily) in comparison with diclofenac (197 patients, 50mg three times daily) in patients with osteoarthritis of the knee. The treatment period of twelve weeks was preceded by a washout period of two weeks duration. At end point, patients in both aceclofenac and diclofenactreated groups exhibited significant improvement in pain intensity (p=0.0001). Although both treatment groups showed significant improvement in all investigators' clinical assessments (joint tenderness, swelling, pain on movement, functional capacity, overall assessment), there were no significant differences between the groups. There was, however, a trend towards greater improvement in complete knee movement and reduced pain on movement with aceclofenac. In patients with initial flexion deformity, aceclofenac was significantly more effective than diclofenac in improving knee flexion after 2–4 weeks of treatment. Patients' subjective assessment of pain relief demonstrated significantly greater efficacy with aceclofenac. At end point, 71% of patients in the aceclofenac group reported improvement in pain intensity as compared to 59% treated with diclofenac (p=0.005). Tolerability of aceclofenac was better than with diclofenac as fewer patients experienced gastrointestinal adverse events. In particular, the incidence of treatment related diarrhoea was less with aceclofenac (1%) than with diclofenac (6.6%). In summary, this study supports a therapeutic role for aceclofenac in arthritis and suggests that it is an alternative NSAID to diclofenac in the treatment of osteoarthritis.     

Effects of strength training on the incidence and progression of knee osteoarthritis

OBJECTIVE: Quadriceps weakness is a risk factor for incident knee osteoarthritis (OA). We describe a randomized controlled trial of effects of lower-extremity strength training on incidence and progression of knee OA. METHODS: A total of 221 older adults (mean age 69 years) were stratified by sex, presence of radiographic knee OA, and severity of knee pain, and were randomized to strength training (ST) or range-of-motion (ROM) exercises. Subjects exercised 3 times per week (twice at a fitness facility, once at home) for 12 weeks, followed by transition to home-based exercise after 12 months. Assessments of isokinetic lower-extremity strength and highly standardized knee radiographs were obtained at baseline and 30 months. RESULTS: Subjects in both groups lost lower-extremity strength over 30 months; however, the rate of loss was slower with ST than with ROM. Compared with ROM, ST decreased the mean rate of joint space narrowing (JSN) in osteoarthritic knees by 26% (P = not significant). However, the difference between ST and ROM groups with respect to frequency of knee OA progression in JSN consensus ratings was marginally significant (18% versus 28%; P = 0.094). In knees that were radiographically normal at baseline, JSN >0.50 mm was more common in ST than in ROM (34% versus 19%; P = 0.038). Incident JSN was unrelated to exercise adherence or changes in quadriceps strength or knee pain. CONCLUSION: The ST group retained more strength and exhibited less frequent progressive JSN over 30 months than the ROM group. The increase in incident JSN >0.50 mm in ST is unexplained and requires confirmation.     

Factor VIII inhibitor in insulin-dependent diabetes mellitus

Acquired factor VIII inhibitor was found in a 69-year-old white male with insulin-dependent diabetes mellitus. He presented with left lower abdominal pain and hematoma after a fall. Preoperative hemostasis studies were normal except for prolonged aPTT. Prolonged aPTT was not corrected by 1:1 mixture with normal fresh plasma and incubation showed further prolongation with time. Factor VIII:c was 3.5%. The inhibitor titer was 7.5 Bethesda units. The possible mechanism causing antibody to factor VIII was postulated to be an autoimmune process and/or increased immunogenicity owing to glycosylation of factor VIII coagulant protein.     

The overall effectiveness of prophylaxis in severe haemophilia

The aim of this retrospective review was to assess the overall effectiveness of prophylaxis when compared with on-demand treatment of haemophilic patients. Twenty-five children (22 with severe haemophilia A and three with severe haemophilia B) were evaluated. Five haemophilia A patients received primary prophylaxis (instituted before the onset of any joint bleed) while the other 17 haemophilia A and all three haemophilia B patients were on secondary prophylaxis. We compared factor usage, number of bleeding episodes, emergency room (ER) visits and hospitalizations while on prophylaxis to those while on demand therapy. All subjects were male, the median age at time of review was 11.4 years and at start of prophylaxis was 4.5 years. Thirteen of the 25 patients (52%) required indwelling venous catheters for access, seven of these had one or more (one-six) episodes of line sepsis. Haemophilia A patients received an average of 23.8 U kg(-1) (20-30 U kg(-1)) of recombinant factor VIII three times a week while haemophilia B patients received 50 U kg(-1) recombinant FIX twice weekly. There was a significant reduction in the mean number of major bleeds on prophylaxis from 15.5 to 1.9 per year and a significant decrease in target joints, ER visits and hospitalizations. Although factor usage per year was higher on prophylaxis, there was an overall reduction in number of bleeds and resultant decrease in hospitalizations and ER visits. By preventing new target joints, prophylaxis can lead to reduction in long-term morbidity and a better quality of life despite increased central lines and higher factor usage.