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1.
M.B. Garvey 《Haemophilia》2002,8(S1):5-8
Development of an inhibitor against factor VIII (FVIII) is an important complication of haemophilia. It occurs in approximately 25–30% of patients with haemophilia A [ 1 ]. FVIII inhibitors may also occur as autoantibodies. The latter occur in nonhaemophiliacs and, although rare (occurring in approximately one per million of the population), are frequently associated with life-threatening bleeding. Inhibitors are considered low level if they are < 5 Bethesda Units (BU) or high level if they are > 10 BU. The former usually remain low and rarely give anamnestic response, the latter do so frequently. Despite various approaches to their management, the presence of inhibitors remains a major cause of morbidity and mortality. The effectiveness of porcine FVIII (pFVIII) in treating patients with both auto- and alloantibodies to FVIII has been well demonstrated when adequate circulating levels of FVIII are obtained [ 2 –10 ]. However, pFVIII therapy may give rise to antibodies to the pFVIII and the utility of this treatment in the presence of high levels of porcine antibody is less well recognized and understood. Nonetheless, pFVIII under these circumstances may be useful in a select group of patients where management is difficult. 相似文献
2.
J. J. Michiels K. Hamulyak H. K. Nieuwenhuis I. Novakova H. H. D. M. van Vliet 《European journal of haematology》1997,59(2):105-109
Abstract: The present study reports on the treatment of bleeding episodes and the natural history of factor VIII inhibitors in 4 patients with acquired haemophilia A postpartum. Low titre type II factor VIII inhibitors in 3 patients and high titre type I inhibitor in 1 patient became apparent immediately to 7 months after delivery. High dose human factor VIII concentrate substitution was effective in controlling bleeding episodes in two cases of factor VIII inhibitor type II, but ineffective in 1 patient with high titre type I factor VIII inhibitor. High dose gammaglobulin intravenously in 1 patient with type II factor VIII inhibitor induced a partial correction of factor VIIIc levels for 2 wk. Immunosuppressive treatment in all 4 patients with acquired haemophilia A postpartum did not reduce the potency of the factor VIII inhibitors. The low titre type II inhibitors spontaneously disappeared in all 3 patients within a few months to 1 yr after discontinuation of the immunosuppressive treatment. The high titre type I factor VIII inhibitor persisted for more than 24 yr. We conclude that immunosuppression in 4 women with acquired haemophilia A postpartum did not significantly affect the factor VIII inhibitor titre. 相似文献
3.
Susan Solymoss 《American journal of hematology》1998,59(1):1-4
Postpartum factor VIII inhibitors are rare; thus, collecting clinical and treatment data may provide valuable information in guiding patient management. This paper reports the results of a survey of United States and Canadian hemophilia centers on 14 patients with postpartum acquired factor VIII inhibitors. Patients ranged in age from 23 to 40 years. Parity at diagnosis was most frequently the first gestation. Two patients were diagnosed prepartum, but two patients only up to one year postpartum. Initial inhibitor titers ranged from two to 550 Bethesda units (BU), and rose to five to 885 BU. The median duration of the inhibitor was 27 months, with two of the 14 inhibitors unresolved at the time of the survey. A total of 80 bleeding episodes occurred, five of which were life or limb threatening. Three patients received no blood products and were not hospitalized. Of those treated for hemostasis, activated prothrombin complex concentrates and porcine factor VIII were most often reported to be effective. For immunosuppression, all patients received steroids and most received additional treatment. Steroids were reported ineffective more frequently than cyclophosphamide. No adverse fetal events were noted and there was no maternal mortality. These results underline the clinical heterogeneity of the severity of postpartum factor VIII inhibitors, and provide treatment guidelines in the absence of prospective studies. Am. J. Hematol. 59:1–4, 1998. © 1998 Wiley-Liss, Inc. 相似文献
4.
Continuous infusion of porcine factor VIII in the management of patients with factor VIII inhibitors
Morel Rubinger Donald S. Houston Nora Schwetz Donna M. M. Woloschuk Sara J. Israels James B. Johnston 《American journal of hematology》1997,56(2):112-118
The effectiveness of continuous infusion porcine factor VIII (PFVIII) has been evaluated in the treatment of 7 consecutive patients with factor VIII(FVIII) inhibitors. Two patients had hemophilia A and five were nonhemophiliacs with acquired FVIII inhibitors. The median pretreatment anti-porcine FVIII titre was 0.2 (range: 0–15.0) Bethesda units (BU), and the anti-human FVIII titer was 12.0 BU (range: 2.4–50.0). All patients presented with major bleeding. Patients were given a bolus dose of PFVIII followed by continuous infusion. Six patients also received immunosuppressive therapy. Therapeutic FVIII levels (>0.5 U/ml) were achieved in 6 of 7 patients at a median time of 12.5 hr, and then maintained with continuous infusion PFVIII. Six patients were treated for more than 7 days, and in four of these there was a decline in FVIII recovery between days 7 to 11, presumably related to a rising antibody response to PFVIII. These four patients were plasmapheresed and the three patients with autoantibodies recovered therapeutic FVIII levels but this did not occur in the patient with hemophilia. Thrombocytopenia developed in 4 patients at days 18 to 24, with the platelet count falling to 11 to 87 × 109/L, and the PFVIII was discontinued in 3 patients. All patients recovered from the acute bleeding events. With prolonged immunosuppressive therapy, the FVIII inhibitor disappeared in all patients with autoantibodies and there have been no relapses after a median follow-up period of 581 days. This study demonstrates that continuous infusion PFVIII is an effective therapy for patients with FVIII inhibitors, but that prolonged treatment is associated with the development of inhibitors to porcine FVIII and severe thrombocytopenia, which readily corrects with discontinuation of PFVIII. Am. J. Hematol. 56:112–118, 1997. © 1997 Wiley-Liss, Inc. 相似文献
5.
Acquired factor VIII inhibitors in nonhemophilic patients 总被引:3,自引:0,他引:3
D. Söhngen C. Specker D. Bach B. M. E. Kuntz M. Burk C. Aul G. Kobbe A. Heyll K. A. Hollmig W. Schneider 《Annals of hematology》1997,74(2):89-93
Antibodies against factor VIII occur in about 15–35% of hemophilia A patients and induce refractoriness to factor VIII substitution.
In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In
very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that
these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical
course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor
VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery.
Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired
or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase.
Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2–128 BU/ml. Immunosuppressive
therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the
inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients
within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy
with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy,
therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone
as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII
concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or
porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.
Received: 23 January 1996 / Accepted: 11 November 1996 相似文献
6.
S. Sallah 《Haemophilia》2004,10(2):169-173
Haemorrhagic manifestations in patients with acquired haemophilia can be fatal if not recognized and treated appropriately. A retrospective analysis of the efficacy of factor eight inhibitor bypassing activity (FEIBA) in patients with acquired haemophilia treated in three medical centres in the past 10 years was conducted. The median inhibitor titre at treatment was 128 Bethesda Units (BU) in patients with severe and 34 BU in patients with moderate bleeding; P = 0.001. The majority of patients received FEIBA at a dose of 75 u kg-1 every 8-12 h. The number of FEIBA doses administered was higher in patients with severe compared with moderate haemorrhage, 10 vs. 6 doses per bleeding episode; P = 0.001. Complete response (CR) was achieved in 76% of severe and 100% of moderate bleeding episodes with a total CR of 86%. When compared with patients with human inhibitor titre <50 BU, those with titre >51 BU at treatment had lower median porcine titre, 1 vs. 9.5 BU; P < 0.05, fewer doses of FEIBA, 6 vs. 8.5 doses; P < 0.05, and shorter time to CR, 29 vs. 42 h; P < 0.05. Patients exposed to factor VIII concentrates prior to FEIBA had significantly higher maximum recorded human inhibitor titre compared with patients without such exposure, 273 vs. 38 BU; P = 0.0001. Treatment with FEIBA was very well tolerated and with very few side effects. This study provides evidence that FEIBA is an effective agent in acquired haemophilia and suitable for all types of patients regardless of severity of haemorrhage, underlying disease or inhibitor titre. 相似文献
7.
E N van den Brink E A Turenhout E C Wijn-Maas F J van der Meer J Voorberg L J Bosch 《Haemophilia》2000,6(6):698-701
We describe a previously healthy woman who at the age of 44 years developed a factor VIII inhibitor, that over the years increased to a maximum level of 3600 Bethesda units (BU) mL(-1) in 1978. The epitope specificity of the factor VIII inhibitor was investigated and antibodies directed against the A2 and C2 domains of factor VIII were detected. The majority of these antibodies were of subclass IgG4. Over the years, the inhibitor titre gradually decreased and in 1989, the inhibitor could no longer be detected. Shortly after, the patient developed autoimmune haemolytic anaemia. A possible link between the disappearance of factor VIII inhibitors and the development of other autoantibodies may be explained by concomitant development of anti-idiotypic antibodies that neutralize the activity of factor VIII inhibitors. We were unable to detect anti-idiotypic antibodies, which could explain the decline in factor VIII inhibitor titre in this patient. 相似文献
8.
Ph. GAUTIER Y. SULTAN† A. PARQUET-GERNEZ‡ F. MERIANE§ C. GUEROIS¶ A. DERLON 《Haemophilia》1996,2(2):88-94
Summary. Using a binding assay to immobilized factor VIII (F VIII) (ELISA) we measured the amount of IgG with binding capacity to FVIII, in the plasma of patients with an inhibitor to F VIII, in multitransfused haemophiliacs without inhibitor and in a control group of blood donors. It was shown that the amount of IgG bound to VIII was elevated in patients with an inhibitor although a weak correlation could be established between the inhibitor titre (BU) and the amount of bound IgG. In all haemophiliacs without inhibitor, IgG bound to F VIII were present. Although the mean value of IgG bound to F VIII was significantly lower than the amount detected in patients with F VIII inhibitors, a group of patients developed an equal amount of IgG recognizing the F VIII molecules to the amount of IgG measured in inhibitor patients. These results indicate that the presence of an inhibitor is not related to the amount of specific IgG bound to F VIII but more likely to the position of epitopes recognized by specific IgG. The presence of IgG bound to F VIII was detected in 92% of control blood donors and an inhibitor to F VIII ranging from 0.5 to 1.3 BU mL-1 in 17% of them. The isotypes of bound immunoglobins were identified in patients and controls: IgG4 subclass was predominant only in patients with an inhibitor and usually associated with antibodies of one or more of the other subclasses. In noninhibitor patients, very few had antibodies of IgG4 subclass with binding capacity to F VIII. These results raised the question of the clinical significance of these antibodies in multitransfused patients. The study indicates that binding assay is a complementary test to be used in multitransfused patients but cannot be used instead of the coagulation tests for detection of inhibitors. 相似文献
9.
Cross-reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand 总被引:2,自引:0,他引:2
J. V. Lloyd A. M. Street E. Berry † J. McPherson H. Ekert A. Lammi W. R. McWhirter E. M. Duncan E. L. Maxwell J. Rowell R. I. Baker M. F. Leahy D. Jupe 《Internal medicine journal》1997,27(6):658-664
Abstract Background: Inhibitory antibodies which neutralise factor VIII develop in 10–20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity.
Aims: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22.
Methods: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A.
Results: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients,1–19% in six, 20–39% in 11 and 40–80% in five. In six of nine patients with acquired haemophilia cross-reactivity was 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor.
Conclusions: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor Vila or prothrombin complex concentrates. 相似文献
Aims: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22.
Methods: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A.
Results: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients,1–19% in six, 20–39% in 11 and 40–80% in five. In six of nine patients with acquired haemophilia cross-reactivity was 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor.
Conclusions: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor Vila or prothrombin complex concentrates. 相似文献
10.
A. BHAVE M.D. Registrar A. SRIVASTAVA M.D. F.R.A.C.P. F.R.C.P.A. Reader V. LEE M.S. Reader A. J. DANIEL M.S. Lecturer D. DENNISON M.D. Associate Professor G. D. SUNDERAJ M.S. M.Ch. F.A.C.S. F.I.C.S. Professor A. SUDARSANAM M.D. Professor 《Haemophilia》1995,1(4):274-276
Replacement therapy in patients with severe haemophilia A is associated with the development of inhibitory antibodies in about 15% [1,2]. The presence of inhibitors of factor VIII greatly complicates and compromises the treatment of these patients because of the lack of any completely satisfactory product to treat them. Haemostatic management for surgery in patients with inhibitors is very difficult. A product frequently used to treat bleeding episodes in such patients is prothrombin complex concentrate (PCC) [3] or its activated derivative (APCC) [4]. Activated recombinant human factor VII is another option [5]. For both these modalities of treatment, there are no laboratory tests that can be used to monitor clinical efficacy [5, 6]. Porcine factor VII is therefore the preferred product for surgery in patients with high-responding factor VIII inhibitors [7]. Unfortunately, none of these products are readily available in most developing countries, including India.
We report the management of a patient with high-responding factor VIII inhibitor using low doses of FEIBAR (Immuno, Austria) in the post-operative period. 相似文献
We report the management of a patient with high-responding factor VIII inhibitor using low doses of FEIBA
11.
Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations 总被引:1,自引:0,他引:1
Summary. During treatment of a haemophilia A patient with a high-responding inhibitor against factor VIII coagulant activity (VIII:C), we observed a difference in recovery of VIII:C depending upon which factor concentrate was infused. Inhibitor plasma samples or IgG fraction from seven patients were tested against a panel of seven different commercially available factor VIII concentrates of which five were plasma-derived and two recombinant. In two of the plasma samples, inhibitor titres manifested a wide range of values depending upon which concentrate was used in the test system. Thus, inhibitor neutralization was less and VIII:C recovery greater when factor VIII concentrates containing large amounts of von Willebrand factor were used than when highly purified concentrates containing no von Willebrand factor or only trace amounts were used. In both of these two patients the inhibitor was directed against the light chain of factor VIII, and it is possible that the epitope of the light chain with which the inhibitor reacts is partly blocked by the von Willebrand factor.
We conclude that inhibitors may differ in their reactivity with factor VIII molecules contained in clotting factor concentrates, and that there is factor VIII epitope variation between different concentrates. These findings have implications for the selection of concentrates for the treatment of inhibitor patients and the haemostatic effect may be improved if a concentrate giving the lowest inhibitor titre is chosen. Thus, in vitro testing of inhibitor reactivity with a panel of concentrates is recommended when treatment of inhibitor patients with factor VIII concentrates is considered. 相似文献
We conclude that inhibitors may differ in their reactivity with factor VIII molecules contained in clotting factor concentrates, and that there is factor VIII epitope variation between different concentrates. These findings have implications for the selection of concentrates for the treatment of inhibitor patients and the haemostatic effect may be improved if a concentrate giving the lowest inhibitor titre is chosen. Thus, in vitro testing of inhibitor reactivity with a panel of concentrates is recommended when treatment of inhibitor patients with factor VIII concentrates is considered. 相似文献
12.
Lusher JM 《Seminars in thrombosis and hemostasis》2000,26(2):179-188
Inhibitor antibodies directed against factor VIII or factor IX present challenges to the clinician. Fortunately, several management options are available, although each has disadvantages as well as advantages. Alloantibodies against factor VIII (which develop in 25 to 50% of children with severe hemophilia A, as well as in a small percentage of children with mild or moderate hemophilia A) may be low titer and transient or may be high titer. Most patients with high-titer problematic inhibitors now try to eliminate the inhibitor by using one of several immune tolerance induction (ITI) regimens. For treatment of bleeding episodes in patients who have high-titer (> or = 5 Bethesda units) inhibitors, one can use a prothrombin complex concentrate (PCC) (preferably an activated PCC [APCC]), recombinant (r) factor VIIa, or porcine factor VIII. The choice of product is generally dependent on the type and severity of the patient's bleeding, degree of cross-reactivity of the patient's inhibitor with porcine factor VIII, physician familiarity with the product, product availability, and cost. In persons with hemophilia B, alloantibodies occur in only 1 to 3% of severely affected individuals. However, in roughly half of those who develop inhibitors, anaphylaxis or severe allergic reactions occur on infusion of any type of factor IX-containing product. This phenomenon usually develops after relatively few exposures to factor IX; thus it is recommended that the first 10 to 20 infusions of factor IX given to children with severe hemophilia B be given in a setting equipped for treatment of shock. For treatment of bleeding episodes in patients with severe allergic reactions, rF VIIa is the treatment of choice. ITI has been less successful in hemophilia B patients with inhibitors than in those with hemophilia A, and in a subgroup of patients with severe allergic reactions who were desensitized to factor IX and then tried on ITI, results were even poorer. Additionally, several developed nephrotic syndrome while on ITI. For hemophilia B patients with inhibitors who do not have allergic reactions to factor IX, bleeding episodes can be treated with PCC or APCC or with rF VIIa. Autoantibodies directed against factor VIII are rare but can occur in a variety of settings. They occur mainly in adults, and bleeding is often severe and life threatening. Although some factor VIII autoantibodies disappear spontaneously, most require immunosuppression. Corticosteroids and cyclophosphamide are generally recommended. For treatment of bleeding, therapeutic options include (human) factor VIII concentrates, porcine factor VIII, APCC, and rFVIIa. The choice of product is generally determined by the consulting hematologist's familiarity with the product, product availability and cost, as well as response to treatment. 相似文献
13.
The treatment of Factor VIII inhibitors remains controversial and no standard therapy exists. We describe in this report two consecutive patients with this inhibitor that responded to cyclosporin. Clinical improvement of the bleeding diathesis, a return to normal of the PTT, a decrease in the level of the inhibitor, and a return to normal of the factor VIII level followed use of this drug. We believe that cyclosporin is effective in the treatment of factor VIII inhibitors and deserves further investigation. Am. J. Hematol. 57:87–88, 1998. © 1998 Wiley-Liss, Inc. 相似文献
14.
M. B. Kleinman 《Haemophilia》2002,8(5):694-697
A 62-year-old African-American man with a history of hypertension, asthma, and prostate cancer, but no prior history of haemophilia presented with gross haematuria following a motor vehicle accident. Coagulation studies revealed a prolonged partial thromboplastin time. Subsequent mixing study and factor analysis confirmed factor VIII (FVIII) deficiency. The patient subsequently developed a knee haemarthrosis associated with persistent haematuria and a profoundly elevated FVIII inhibitor titre. Fresh frozen plasma was initiated upon presentation. Once FVIII inhibitor was discovered, immunosuppressive agents were started. Concurrent treatment with acute bypass agents including porcine FVIII, and recombinant human factor VIIa (rFVIIa;NovoSeven), was also given. Ultimately, anti-inhibitor coagulant complex (Autoplex T) was administered, stabilizing the haematuria and haemarthrosis. There was no additional bleeding 6 months after the last dose of anti-inhibitor coagulant complex. This case is consistent with others in which anti-inhibitor coagulant complex therapy was used successfully to manage patients with serious acute bleeding problems who are found to have acquired inhibitors to factor VIII. 相似文献
15.
R. Winikoff A. Boulanger P. Robinson † J. ST-Louis ‡ S. Lacroix G.-É. Rivard 《Haemophilia》2003,9(1):104-109
The use of porcine factor VIII (FVIII) (Hyate:C, Ipsen) has proven to be very successful in treating patients with FVIII inhibitors. The best way to predict the usefulness of porcine FVIII therapy, and/or to estimate the appropriate treatment dose in a given patient, is to measure the patient inhibitor titre against porcine FVIII with the Bethesda assay, using porcine FVIII as the source of FVIII in the assay. The goals of the present study were to (1) find the optimal storage temperature, diluent and concentration for a working solution of porcine FVIII to be used as the source of FVIII for the porcine Bethesda assay, (2) assess the reliability of the labelled FVIII units in the preparation of such working solutions of porcine FVIII and (3) compare the inhibitor titres determined by the Bethesda assay using both porcine and human standard reference curves for measuring residual FVIII. The results of the present study demonstrate that a ready-to-use working solution of 1 U mL(-1) of Hyate:C diluted in human FVIII deficient plasma, either containing or deficient in von Willebrand factor antigen, is stable for up to 12 months, at -20 degrees C. The preparation of the 1 U mL(-1) working solution could be reliably calculated based on the units indicated on the vial label. Finally, using the human standard curve yields similar results to using the porcine standard curve for measuring any titre of allo- or auto-antibody against FVIII in the Bethesda assay, using Hyate:C as the source of FVIII. These findings are of practical value when performing a porcine FVIII-based Bethesda assay. 相似文献
16.
The authors examined the efficacy of 2-chlorodeoxyadenosine (2-CDA) in the treatment of refractory inhibitors to factor VIII in persons without hemophilia. The drug was administered to 6 patients at a dose of 0.1 mg/kg as a 24-hour continuous infusion for a total of 7 days each cycle. An average of 3 immunosuppressive regimens per patient had been administered prior to enrollment in this study. The median inhibitor titer against human and porcine factor VIII before treatment with 2-CDA was 31 Bethesda units (BUs) and 9 BU, respectively. The median inhibitor titer against human and porcine factor VIII after treatment was 3.5 BU and 1.5 BU, respectively. The median time to reach nadir inhibitor titer in this study was 137 days, whereas the median time to reach a 50% increase in factor VIII was 117 days. No major toxicity was observed in any patient in this study. Patients with acquired inhibitors to factor VIII refractory to conventional immunosuppressive therapy may respond favorably to 2-CDA. 相似文献
17.
C. H. Miller 《Haemophilia》2018,24(2):186-197
Inhibitors are antibodies directed against haemophilia treatment products which interfere with their function. Factor VIII (FVIII) inhibitors in haemophilia A and factor IX (FIX) inhibitors in haemophilia B are significant clinically when they require a change in a patient's treatment regimen. Their persistence may increase morbidity and mortality. Multiple laboratory tests are now available for detecting and understanding inhibitors in haemophilia. Inhibitors are traditionally measured by their interference in clotting or chromogenic factor assays. They may also be detected using immunologic assays, such as enzyme‐linked immunosorbent assay or fluorescence immunoassay. Anti‐FVIII or anti‐FIX antibodies of IgG4 subclass best correlate with the presence of functional inhibitors. Improvements in inhibitor measurement have been recently introduced. Preanalytical heat treatment of patient specimens allows testing of patients without delaying treatment. Use of chromogenic and immunologic assays may aid in identification of false‐positive results, which are frequent among low‐titre inhibitors. Validated reagent substitutions can be used to reduce assay cost. New methods for defining assay positivity and reporting low‐titre inhibitors have been suggested. Challenges remain in the areas of quality control, assay standardization, monitoring of patients undergoing immune tolerance induction therapy and testing in the presence of modified and novel treatment products. 相似文献
18.
Acquired factor VIII (FVIII) inhibitors are a rare cause of coagulopathy which are associated with a high mortality rate. Treatment of bleeding episodes is often difficult and may vary with the degree of titre elevation. Individuals with very high-titre antibodies [>100 Bethesda units mL(-1) (BU)] may have difficulty achieving a complete sustained remission and, consequently, various treatments including immunosuppression, cytotoxic chemotherapy and plasmapheresis have been reported. Rituximab is an anti-CD20 monoclonal antibody which has demonstrated efficacy in the treatment of individuals with acquired FVIII inhibitors, however there is limited data in the subgroup of patients with inhibitor titres >100 BU. In this study, we present four patients with acquired FVIII inhibitor titres >100 BU who were resistant to initial therapy with cyclophosphamide, vincristine and prednisone. The patients' inhibitor titres ranged from 249 BU mL(-1) to 725 BU mL(-1) and all received 4 weekly infusions of rituximab at 375 mg m(-2). Each patient partially responded to rituximab therapy with an improvement in inhibitor titres and FVIII activity, however, three of the four patients relapsed thereafter. The individual who did not relapse achieved a partial response for 13 months and then died of causes unrelated to her coagulopathy. We conclude that in patients with acquired FVIII inhibitors and titres >100 BU, treatment with rituximab alone is effective but not sufficient to achieve a sustained response. Rituximab in combination with other therapies may provide a better result in this high-risk population. 相似文献
19.
A. V. PATHARE S. GHAMANDE S. FERNANDES S. BHATIA F. JIJINA S. SHETTY K. GHOSH & D. MOHANTY 《Haemophilia》1997,3(3):212-214
Summary . The present report describes two unusual cases of bleeding due to development of inhibitor against factor VIII. One of the patients was known to have severe haemophilia B (factor IX < 1%) and the other, a healthy male of 46 years, spontaneously started to bleed and was found to have developed inhibitors to factor VIII:C along with other autoantibodies. Development of inhibitors to coagulation factors is a serious clinical problem in de-veloped countries and is more so in developing countries where treatment options are often limited. 相似文献
20.
Prompt immune tolerance induction at inhibitor diagnosis regardless of titre may increase overall success in haemophilia A complicated by inhibitors: experience of two US centres
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C. Nakar M. J. Manco‐Johnson A. Lail S. Donfield J. Maahs Y. Chong T. Blades A. Shapiro 《Haemophilia》2015,21(3):365-373
Current guidelines recommend delaying the start of immune tolerance induction (ITI) until the inhibitor titre is <10 Bethesda units (BU) to improve success. This study was conducted to evaluate ITI outcome relative to time to start ITI from inhibitor detection irrespective of inhibitor titre. Data were retrospectively collected from two US haemophilia treatment centres (HTCs) on subjects with severe/moderate factor VIII (FVIII) deficiency with inhibitors who underwent ITI. Outcomes were defined pragmatically: success – negative inhibitor titre and ability to use FVIII concentrate for treatment/bleed prevention; partial success – inhibitor titre 1 to <5 BU with ability to use FVIII concentrate for treatment of bleeding; failure – ITI ongoing >3 years without achieving success/partial success, or ITI discontinuation. Fifty‐eight subjects were included; 32 of 39 (82%) with high‐responding inhibitor (HRI) achieved success, 7 failed. HRI subjects were subdivided based on ITI start time: 23/39 subjects started within 1 month of detection and 22/23 (96%) achieved success. Of these 23, 13 started ITI with an inhibitor titre ≥10 BU; all were successes. Eleven of 39 HRI subjects had an interval >6 months until ITI start; 7 (64%) achieved success. Time from inhibitor detection to ITI start may play a critical role in outcome. A titre ≥10 BU at ITI start did not influence outcome in subjects when ITI was initiated within 1 month of detection. Prompt ITI should be considered a viable therapeutic option in newly identified patients with inhibitors regardless of current inhibitor titre. 相似文献