Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease: Results from 3WINTERS-IPS, an international and collaborative cross-sectional study.

BACKGROUND: Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. AIMS: To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. METHODS: We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. RESULTS: In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels < 20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. CONCLUSIONS: In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.

Effect of Pulsed Electromagnetic Fields on Clinical Signs and Quality of Life in Patients with Hemophilic Arthropathy of the Knee Joint: A Randomized Controlled Trial.

BACKGROUND: Hemophilic arthropathy (HA) causes severe joint damage and impairs the quality of life (QoL) of hemophiliacs. This study was undertaken to evaluate the effect of pulsed electromagnetic fields (PEMFs) on the clinical signs and QoL of patients with severe hemophilia A experiencing moderate HA in the knee joint. MATERIALS AND METHODS: Thirty-six severe hemophiliacs with HA of the knee joint were randomly assigned into the PEMF (n = 20) or placebo (n = 16) groups. The PEMF group received 60 min of PEMF (2 Hz, 25 Gauss for 30 min and 70 Hz, 30 Gauss for 30 min) on the knee joint, three times per week for 6 weeks. The clinical signs, QoL, and pain intensity were measured by the Hemophilia Joint Health Score, A36 Hemofilia-QoL Questionnaire, and visual analog scale, respectively, before and after treatment. RESULTS: In the PEMF group, a significant difference before and after intervention in terms of clinical signs, QoL, and pain intensity (P < 0.05) was founded. Between-group analysis showed a significant improvement in clinical signs (except for atrophy, strength, and swelling duration), QoL, and pain intensity in the PEMF versus control group (P < 0.05). CONCLUSIONS: PEMF can improve the clinical signs, QoL, and pain intensity of severe hemophilia A patient with moderate knee hemophilic arthropathy.

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients.

BACKGROUND: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. METHODS: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA® , Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. RESULTS: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. CONCLUSIONS: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.

Effects of short-term resistance training and pulsed electromagnetic fields on bone metabolism and joint function in severe haemophilia A patients with osteoporosis: a randomized controlled trial.

OBJECTIVES: To assess the effects of short-term resistance training and pulsed electromagnetic fields on bone metabolism and joint function in patients with haemophilia with osteoporosis. DESIGN: A randomized, controlled, patient and blood sample assessor-blinded, six-week trial, three times weekly. SETTING: Hospital outpatients with severe haemophilia A and osteoporosis. SUBJECTS: Forty-eight patients were randomly assigned to resistance training (RT, n = 13), combined resistance training with pulsed electromagnetic fields (RTPEMF, n = 12), pulsed electromagnetic fields (PEMF, n = 11) and control (n = 12) groups. INTERVENTION: The RT group received 30-40 minutes of resistance exercises and placebo pulsed electromagnetic fields. The RTPEMF group received the same exercises with lower repetition and 30 minutes of pulsed electromagnetic fields. The PEMF group was exposed to 60 minutes of pulsed electromagnetic fields (30 Hz and 40 Gauss). MAIN MEASURES: Bone-specific alkaline phosphatase, N-terminal telopeptide of type 1 collagen, and joint function, using the modified Colorado Questionnaire, were measured before and after the programme. RESULTS: The absolute change of bone-specific alkaline phosphatase was significant in the RT and RTPEMF groups compared with the control group (25.41 ± 14.40, 15.09 ± 5.51, and -4.73 ± 2.93 U/L, respectively). The absolute changes in the total score for joint function were significant for knees, ankles, and elbows in the RT group (9.2 ± 1.38, 5.1 ± 0.5, and 3.2 ± 0.8, respectively) and the RTPEMF group (7.7 ± 1.0, 3.3 ± 0.6, and 2.5 ± 0.7, respectively) compared to the PEMF and control groups. This value was significant for knee joints in the PEMF group compared to the control group (3.4 ± 0.5 and 0.66 ± 0.4, respectively). CONCLUSIONS: Resistance training is effective for improving bone formation and joint function in severe haemophilia A patients with osteoporosis.

Evaluation of iron status by serum ferritin level in Iranian carriers of beta thalassemia minor.

BACKGROUND: Conflicting data exists on iron metabolism in adults with beta thalassemia minor (BTM). The purpose of this study was to evaluate the serum ferritin (SF) levels in Iranian adults with BTM in order to determine the iron status in these subjects. METHODS: Eighty four (41 males, 43 females) Iranian adults with BTM and 102 (55 males, 47 females) healthy subjects as a control group were enrolled in the study. SF level was measured by immunoradiometric assay (IRMA). RESULTS: The mean SF concentration in the BTM group was 101.84+/-8.5 microg/L, which was higher than the mean SF in non-BTM subjects (67.98+/-5.4 microg/L, p=0.001). Comparing SF concentrations between BTM males and males in the control group showed that the SF level was significantly higher in BTM males (150.57+/-75.13 microg/L vs. 96.66+/-56.79 microg/L, p<0.001). Similar data was found for females (55.38+/-47.94 microg/L in the BTM group vs. 34.42+/-25.72 microg/L in the non-BTM group, p=0.01). CONCLUSION: This study showed that BTM may play a role in improving iron status in females with BTM. However in males, BTM can lead to iron overload. Therefore, we suggest determining the levels of SF in subjects with BTM, especially in males, to avoid harmful effects of iron overload in early stages of the disorder.

Thalassemia in Iran: epidemiology, prevention, and management.

PURPOSE: To determine the prevalence and geographic distribution of thalassemia and to evaluate the success of the thalassemia prevention and treatment programs in Iran. METHODS: Data were obtained from the National Thalassemia Registry of Iran, Iranian Blood Transfusion Organization, genetic laboratories involved in prenatal diagnosis, related pharmaceutical companies, and centers performing bone marrow transplantation for thalassemic patients. RESULTS: A total of 13,879 living patients have been registered, mostly from the northern and southern parts of Iran with the median age of 15 years. Twenty-three percent of patients were older than 20 years. The number of newly diagnosed cases has been decreased considerably after the start of the prevention program. Since the introduction of prenatal diagnosis, 2819 couples (2549 fetuses) have been tested, with only 6 false results. Elective abortion was not performed in 10 affected fetuses. Most common mutations detected were IVS II-1 and IVS I-5. In 2003, approximately 25% of the national blood products and 6 million vials of desferal were used for thalassemic patients. Overall, 340 patients have received allogeneic bone marrow transplantation, of those 46 patients deceased. Bloodborne infections have also been decreased significantly owing to the national screening of blood products for bloodborne viral infections. DISCUSSION: Owing to the national prevention program and provided special care, the age distribution of thalassemic patients in Iran is getting adapted to a full prevention and treatment program and life expectancy of these patients has been increased considerably. This shift in the age distribution of thalassemia, a traditionally considered pediatric disease, will face us with new challenges and the health care system should be prepared for this new face of thalassemia.