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1.
Kasper  CK; Boylen  AL 《Blood》1985,65(1):211-213
We gave danazol (600 mg/day orally for 14 days) to eight adults with mild or moderate hemophilia A, one with severe hemophilia A, and one with moderate hemophilia B. In the patient with severe hemophilia A, the levels of factor VIII two to four days after an infusion of factor VIII concentrate were higher than expected, suggesting a prolonged half- life. In one patient with mild hemophilia A, a questionable slight increase in factor VIII was noted at the end of the study. No change was seen in factor levels of other subjects. Therapy was terminated early, at eight days, in a patient who developed severe muscle cramps, and at ten days in a patient with a severe rash. Another patient developed hepatic dysfunction three days after completing the 14-day trial. In this trial, the side effects of danazol outweighed its meager and questionable benefits.  相似文献   

2.
Saidi  P; Lega  BZ; Kim  HC; Raska  K Jr 《Blood》1986,68(3):673-679
Several recent studies have reported conflicting results on the effectiveness of danazol, an attenuated androgen, in raising plasma levels of clotting factors VIII and IX in patients with hemophilia. We undertook a randomized, double-blind cross-over trial using 8 weeks' administration of danazol (D), 600 mg/d, and 8 weeks' administration of placebo (P) separated by 2 weeks of rest in 12 patients with hemophilia A and four patients with hemophilia B. Plasma factor VIII and IX levels, frequency and type of bleeding episodes, amount of factor concentrate infused, fibrinogen, fibrinolysis assays, antithrombin III, liver function, and immune parameters were followed. During the danazol phase a minimal increase was noted in the average clotting factor levels, an increase that, although statistically significant, was of hemostatically marginal magnitude. Significant increases in protein C and plasminogen levels, however, were observed during the danazol period, suggestive of danazol-mediated enhanced fibrinolysis. Clinically, bleeding frequency was significantly increased, and more clotting factor was consumed during the danazol period. Furthermore, eight episodes of hematuria and oral mucosal bleeding was reported during the danazol phase in contrast to only one episode of hematuria during the placebo phase, consistent with an enhancement of fibrinolytic activity with danazol. We conclude that danazol does not have a hemostatically significant effect on plasma levels of factor VIII and IX but may be associated with enhancement of fibrinolytic activity, resulting in increased bleeding frequency and requiring more clotting factor infusions. Therefore, danazol is not a viable alternative in the treatment of hemophilia.  相似文献   

3.
L M Hu  L L Ye  B Xu 《中华内科杂志》1990,29(2):85-7, 125
20 cases of hemophilia, including ten of hemophilia A , nine of hemophilia B and one of von Willebrand's disease (VWD), were treated with ranitidine. The results revealed that the levels of both factor VIII and IX were increased and the clinical symptoms of bleeding were ameliorated. The level of factor VIII in hemophilia A ranged from 5.27 +/- 3.94% before treatment and rose to 14.68 +/- 4.70% during the treatment period (P less than 0.001). The level of the factor IX in the patients with hemophilia B increased from 4.42 +/- 3.01% before treatment to 20.33 + 9.31% under treatment (P less than 0.001). Tn the patient with VWD the level of the factor VIII rose but the level of von Willebrand factor did not change. The drug has no side effect. The results of our study suggests that ranitidine therapy is effective and safe in hemophilia.  相似文献   

4.
Seven patients with hemophilia A and B and 3 patients with acquired hemophilia were treated on 13 and 4 occasions, respectively, with protein A immunoadsorption to reduce anti-factor VIII or IX antibodies. Usually the patients were treated on 2 consecutive days. On each treatment day an average of 3 (range: 1.02-5.83) plasma volumes were processed in the congenital patients and 1.5 (range: 1.02-2.90) in those with acquired hemophilia. Plasma levels of IgG decreased from 18.9 +/- 1.9 to 3.1 +/- 1.2 g/l in the congenital group, and from 11.5 +/- 2.3 to 2.3 +/- 0.6 g/l in the acquired group. In the congenital hemophiliacs a corresponding reduction in inhibitor level of 70-95% was regularly seen; in 1 exceptional patient the inhibitor was reduced from 4,350 to 12 Bethesda Units/ml (BU/ml) during 5 days of treatment. In the congenital hemophiliacs immunoadsorption was followed by factor infusion to peak levels between 8 and 215 IU/dl. In the patients with acquired hemophilia a satisfactory reduction in inhibitor levels was obtained in 2 of the 4 treatments, which were followed by DDAVP or factor infusion. Some recommendations for the use of protein A immunoadsorption in the treatment of hemophilic patients will be given.  相似文献   

5.
Danazol treatment of idiopathic myelofibrosis with severe anemia   总被引:1,自引:0,他引:1  
BACKGROUND AND OBJECTIVE: Severe anemia is an important problem in patients with idiopathic myelofibrosis (IM). When other therapeutic measures are unsuccessful or not applicable, 40-50% favorable responses are obtained with androgen therapy. Oxymetholone is the drug usually employed, but good results have also been reported with danazol, although the experience is limited to a few patients. The aim of the present study was to evaluate the effect of danazol on the anemia of IM. DESIGN AND METHODS: Seven out of 22 consecutive IM patients were eligible for danazol treatment because of severe anemia not treatable with (four cases) or refractory to (three cases) other therapies. Danazol (600-800 mg/day) was given orally for six months and thereafter progressively tapered to the minimum effective dose in responding patients or discontinued in non-responders. Complete response was considered cessation of transfusion requirements with normalization of hemoglobin (Hb) values; partial response was defined as a > 30% reduction in transfusional needs or an increase > 10 g/L in the Hb. The effect on platelet counts was also analyzed. RESULTS: One patient splenectomized three years earlier achieved a complete response and three a partial response, giving an overall response rate of 57 %. A significant increase in platelet counts was also observed in three responders. The responses were first seen between three and six months after the start of treatment, which was usually well tolerated. INTERPRETATION AND CONCLUSIONS: Danazol, given at an appropriate dosage for a sufficient time, is an effective treatment for a substantial proportion of IM patients with severe anemia without marked splenomegaly or who have been previously splenectomized.  相似文献   

6.
STUDY OBJECTIVE: To assess the long-term benefit and side effects of danazol therapy, and to delineate factors influencing the responses in patients with autoimmune thrombocytopenia. DESIGN: Before and after trial. SETTING: Referral-based hematology clinics and the University of Miami teaching hospitals. PATIENTS: Data were collected on 96 patients (60 women and 36 men, 45 of whom had had splenectomies) receiving danazol therapy for autoimmune thrombocytopenia and analyzed. INTERVENTION: Danazol was added to the previous therapy or begun as an initial therapy. Glucocorticoids were tapered gradually. MEASUREMENTS AND MAIN RESULTS: The overall response rate to danazol was 61.4%. Among responders, the platelet counts (mean +/- SD) before and after danazol treatment were 36 +/- 24 x 10(9)/L and 145 +/- 77 x 10(9)/L, respectively, and the time to response was 2.7 +/- 3 months. Sex, age, and the status of the spleen (absent or present) influenced the responses to danazol. In women, but not in men, response rates improved with advancing age, especially in the nonsplenectomized women. This may be because estrogen levels are high in younger women and low in older women and men. Danazol, when given longer than a year, induced remissions lasting for years even after its discontinuation, but early relapses were frequent when danazol was administered for less than 6 months. Platelet-associated IgG returned to normal range during unmaintained remission. CONCLUSION: Danazol is best suited for long-term medical management of autoimmune thrombocytopenia. It is well tolerated, and lasting, unmaintained remissions often occur after prolonged danazol administration. Age, sex, and the status of the spleen influence the responses. When danazol therapy is used, glucocorticoids can be substantially reduced in dosage or withdrawn. Danazol is a good alternative to splenectomy in elderly persons, especially in women.  相似文献   

7.
Liver transplantation in hemophilia A   总被引:14,自引:3,他引:14  
Four patients with hemophilia A have undergone liver transplantation in our institution, three successfully. The first was a 21-year-old man with chronic active hepatitis (CAH) in whom the effects of previous abdominal operations prevented the satisfactory technical insertion of the new liver. He died intraoperatively. The second patient was a 15- year-old boy with CAH who began to synthesize factor VIII coagulant activity (F VIII:C) within 18 hours of successful liver transplantation and has continued to do so for almost 2 years (F VIII:C range 0.89 to 3.20 U/mL). The first 2 months of his postoperative course were complicated by infections, but since that time he has done well and has returned to school. The third patient was a 48-year-old man with portal fibrosis and severe ascites. He synthesized F VIII:C (range 0.96 to 1.50 U/mL) within six hours after reestablishment of circulation through the new liver. His postoperative course was complicated by numerous infections, and he died with sepsis and an acquired immunodeficiency-like syndrome 4 months after transplantation. The fourth patient was a 47-year-old mild hemophiliac with CAH who produced adequate factor VIII:C levels following transplantation (range 0.79 to 2.80 U/mL). These patients demonstrate that liver transplantation in hemophiliacs with end-stage liver disease may be lifesaving and results in correction of the F VIII:C deficiency and associated hemorrhagic tendency.  相似文献   

8.
In vitro and in vivo Characterization of Factor VIII Preparations   总被引:3,自引:0,他引:3  
Abstract. An in vitro and in vivo comparison of nine commercial and noncommercial factor VIII preparations was made. These consisted of one lyophilized cryoprecipitate, four intermediate (IPC) and four high purity concentrates (HPC). Protein, fibrinogen, factor VIII complex, IgG, IgM and anti-A and B alloagglutinins levels were measured. These three qualities of product were defined by two ratios: units of F VIII: C per mg of protein and per mg of fibrinogen. They were, respectively, <0.5 and < l in cryoprecipitate, 0.5-1 and 1–3 in IPC, and >1 and >3 in HPC. The F VIII:C/F VIII:AG ratio ranged from 0.3 to 0.6 and the F VIII: C/F VIII: VWF ratio was always lower than 1. Varying titers of alloagglutinins were found, unrelated to either IgG or IgM levels. Seven of these preparations were injected into several classical hemophilia A patients for treatment of minor hemorrhages. The peak of F VIII: C activity was always found 1 h postinjection. The F VIII: C recovery ranged from 80 to 140% and the half-life from 8 to 15 h. No significant difference was found among these products and the clinical efficacy was similar.  相似文献   

9.
In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.  相似文献   

10.
Summary Desmopressin acetate (1-desamino-8-Darginine vasopressin, DDAVP) has mostly been given by the parenteral route for the treatment of mild hemophilia A and von Willebrand's disease type I. In the present study the hemostatic effects of desmopressin acetate administered intranasally by spray in a dose of 300µg and intravenously 0.3–0.4µg/kg were assessed and compared in 8 patients with hemophilia A and 22 patients with von Willebrand's disease type I. A bioequivalent response to intravenous and intranasal desmopressin acetate was found in Factor VIII coagulant activity (VIII:C) in the hemophilia patients. In the von Willebrand patients, an equivalent shortening of the bleeding time was seen after the two modes of administration, even though intravenous injection gave a higher increase in plasma levels of VIII:C and vWF:Ag. In five patients with von Willebrand's disease the duration of the spray effect on VIII:C and vWF:Ag was followed for 24 h. After 12 h the mean level of VIII : C was 1.4, and of vWF:Ag 1.5, times the basal level. The findings suggest that the spray can be recommended for home or prophylactic treatment of patients with mild hemophilia A and von Willebrand's disease.  相似文献   

11.
Disorders of coagulation in children often prove challenging to the medical care team. The aims of this study were to assess the spectrum and prevalence of coagulation disorders among children attending Mansoura University Children Hospital (MUCH), Mansoura, Egypt. A total of 105 pediatric patients were referred to MUCH. They were divided into two groups: congenital coagulation disorders (75 cases, age 45.36 +/- 48.59 months), and acquired coagulation disorders (30 cases, age 56.13 +/- 61.61 months). All patients were subjected to thorough history taking including the nature of bleeding, family, past history, mode of inheritance, and detailed physical findings. Hemostatic tests included: platelet count, bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT). Specific tests in the congenital group include assay of coagulation factors according to each disorder, Von Willebrand factor assay, ristocetin aggregation test, APTT mixing study for detection of inhibitors in complicated hemophilia cases, F VIII C to VWAg ratio with cut off 0.7 for detection of carriers in some hemophilia A families. Congenital disorders constituted 71.4% of the studied cases vs. 28.6% for acquired disorders. Hemophilia A (42.85%), hemophilia B (14.28%) and liver diseases (14.28%) represented the majority of the studied cases. Mild and moderate cases of hemophilia A and B are more frequent than severe cases in both types. Male sex is more frequent than female in the congenital group (94.7 vs. 5.3%, P < 0.001). Direct correlation existed between factor level assay and severity of hemophilia (r = 0.73, P = 0.006). Three mothers and one sister were identified as carrier out of four families. Anti-clotting factors inhibitor was detected in 18.2% of patients with hemophilia A and in 9.1% with hemophilia B. In conclusion, our study found that hemophilias are the most prevalent congenital coagulation disorders among children. Attention must be given for detection of hemophilia carriers and inhibitors of clotting factors.  相似文献   

12.
A 53-year-old man was admitted with impairment of breathing following laryngeal edema. Serum levels of CH50 (22 U/ml), C4 (3 mg/dl), C1-INH protein (10.6 mg/dl) and C1-INH activity (LT 25%) were low. Complement study of the patient's family members revealed that he was one of 5 patients in 3 generations with hereditary angioneurotic edema (HANE). Administration of the androgen derivatives Danazol (600 mg/day) and Oxymetholone (30 mg/day) effectively increased serum levels of C1-INH activity and C4. Though eruption and hepatic dysfunction attributable to administration of the drugs appeared, these side effects improved after withdrawal of the drugs. Subsequently, the treatment with Danazol at a low dose (100 mg/day) was resumed, and the patient has had no episodes of edema for the past 3 years. Regarding the familial cases of HANE, fewer than 20 have been reported in Japan.  相似文献   

13.
Rodeghiero  F; Castaman  G; Di Bona  E; Ruggeri  M 《Blood》1989,74(6):1997-2000
The consistency in time of responses to separate desmopressin (DDAVP) infusions in patients with von Willebrand's disease (vWD) and mild or moderate hemophilia A has been the subject of limited investigation. We report here the results of a clinical study undertaken to test the consistency of responses to repeated DDAVP administrations in 22 patients with vWD and 10 with mild or moderate hemophilia A (time interval between first and last infusion ranging from 1 to 77 months; median, 13 months). In patients with vWD, 80% of cases showed a departure of less than 20% from the average VIII:C peak level calculated after the two infusions. A similarly consistent pattern was observed for bleeding times recorded 30 minutes after each infusion. In patients with hemophilia A, some infused on more than two instances, the departure from the average VIII:C peak level was less than 20% in nearly 70% of cases. A good within-family consistency was also demonstrated by analyzing data obtained from seven kindreds with vWD and two with hemophilia A. In conclusion, our study suggests that the pattern of responsiveness observed after a DDAVP test-infusion can be reliably used to decide the future clinical management of the individual patient and that a similar pattern of response is usually observed within the same kindred.  相似文献   

14.
We present a case of a 74-year-old male, who had a relapse of minimal change nephrotic syndrome (MCNS) as the initial presentation of acquired hemophilia A. MCNS had been maintained in remission with prednisolone 10 mg for 15 years. In early December 2005, the patient developed edema of the right leg, was admitted to a local general hospital, and was diagnosed as having a relapse of MCNS based on massive proteinuria (urine protein 6.1 g/day). One week later, severe anemia (hemoglobin 4.4 g/dl) and acute renal failure (creatinine 2.0 mg/dl) developed, and a CT scan of the abdomen revealed a hematoma in the left iliopsoas muscle. He was referred to our hospital with bleeding tendency. Laboratory examination revealed prolonged APTT 80.5 seconds), reduced factor VIII activity (<1%) and thepresence of factor VIII inhibitor at a titer of 19 Bethesda units/ml, based on which he was diagnosed as having acquired hemophilia A. With recombinant activated FVII, hemostasis was obtained and prednisolone administration 60 mg/day (1 mg/kg) was started. Both the acquired hemophilia A and MCNS responded well to the treatment with prednisolone. Six weeks after initiation of the treatment, factor VIII inhibitor and urine protein disappeared. This patient is considered to be a rare case; to the best of our knowledge, this is the third report of acquired hemophilia A with nephrotic syndrome.  相似文献   

15.

Background

Platelets are an underappreciated factor in the classification of the bleeding tendency of patients with hemophilia. In this cross-sectional study, we investigated platelet activation status and responsiveness in relation to residual factor VIII activity and, within the group with severe hemophilia (<1% residual factor VIII activity), to annual factor VIII consumption.

Design and Methods

Twenty-one patients with mild-moderate hemophilia A, 13 with severe hemophilia A and 21 healthy controls were studied. The basal level of platelet activation and platelet responsiveness to activation and inhibition were determined by the measurement of platelet P-selectin expression and soluble platelet activation markers.

Results

Patients with severe hemophilia A had a higher percentage of activated platelets at baseline (15.9%) when compared to patients with mild-moderate hemophilia A (8.2%, P=0.014) and controls (6.4%, P<0.001). Both patients with mild-moderate hemophilia A and those with severe hemophilia A had higher levels of the soluble platelet activation markers platelet factor 4 (1.4 and 1.8 pg/106 platelets), CXCL7 (65.8 and 48.2 pg/106 platelets) and RANTES (12.8 and 9.5 pg/106 platelets), compared to controls (platelet factor 4: 0.3 pg/106 platelets, P<0.001 and <0.001; CXCL7 20.0 pg/106 platelets, P<0.001 and <0.001; RANTES 4.5 pg/106 platelets, P<0.001 and =0.003, respectively). In support of these observations, we found clinical evidence that higher platelet P-selectin expression correlates with lower factor VIII consumption in patients with severe hemophilia (Spearman’s r −0.65, P=0.043).

Conclusions

This study indicates that platelets from patients with severe hemophilia A are in a pre-activated state and that this pre-activated state is associated with factor VIII consumption.  相似文献   

16.
Determinants of plasma factor VIIa levels in humans   总被引:1,自引:0,他引:1  
Several enzymes can activate factor VII in vitro, but the protease responsible for generating factor VIIa in vivo has not been determined. Using recombinant tissue factor that has undergone a COOH-terminal truncation, a sensitive functional assay has been established for measuring plasma factor VIIa levels. To evaluate the mechanism responsible for the generation of factor VIIa in vivo, we measured the levels of this enzyme after administering purified concentrates of factor IX and factor VIII to patients with severe deficiencies of these clotting factors. In patients with hemophilia B, factor VIIa levels were initially reduced to 0.5 +/- 0.1 ng/mL and gradually increased to normal after infusing 100 U/kg of body weight (BW) of factor IX. Despite these increases, there were no significant changes in the generation of factor Xa or thrombin. In patients with hemophilia A, only a slight reduction in factor VIIa levels (2.5 +/- 1.3 ng/mL) was observed as compared with controls (3.3 +/- 1.1 ng/mL) and no significant changes were observed after factor VIII levels were normalized. The administration of recombinant factor VIIa (10 micrograms/kg BW) to patients with factor VII deficiency increased the mean circulating level of the enzyme to 118 ng/mL, but this only resulted in normalization of the levels of the activation peptides of factor IX and factor X. The above data indicate that factor IXa is primarily responsible for the basal levels of free factor VIIa generated in vivo (ie, in the absence of thrombosis or provocative stimuli) and that changes in the plasma concentrations of free factor VIIa in the blood do not necessarily lead to alterations in the extent of factor X activation.  相似文献   

17.
Danazol was administered orally at a dosage of 50 mg/day to 17 patients (11 females and 6 males) with idiopathic thrombocytopenic purpura refractory to steroids and/or splenectomy. The patients had not been treated with conventional dosages of danazol. The drug was suspended in four patients because of adverse effects of danazol. In 13 patients (8 females and 5 males, mean age 44 y. o.) who received the danazol therapy for more than 6 months, there were no patients with an excellent response, and one patient had a good response to the therapy. The rest of the patients did not respond to danazol.  相似文献   

18.
Fourteen patients with idiopathic thrombocytopenic purpura (ITP) refractory to steroids and/or splenectomy were treated with danazol (200 mg 3 times a day) for 2 months. The following responses were achieved: excellent (platelet count greater than 100 X 10(9)/l) in 5 patients; good (greater than 50 X 10(9)/l, but less than 100 X 10(9)/l) in 2 patients, and poor in (no increase of platelet count) 7 patients. In three cases remission lasted more than 7 months. Danazol was well tolerated and in most patients better suited than steroids for long-term intake.  相似文献   

19.
Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).  相似文献   

20.
Conventional clotting factor concentrates have, until recently, been "of intermediate purity," containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.  相似文献   

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