摘要:

AbstractA microspectrophotometric technique was used to measure the kinetics of methemoglobin reduction in intact, unaltered human erythrocytes. Reduction was catalyzed by endogenous NADPH‐methemoglobin reductase in the presence of Nile Blue. The technique was applied to the study of erythrocytes from a female donor with decreased glucose‐6‐phosphate dehydrogenase (G‐6‐PD) activity. The individual was shown to be heterozygous for deficiency of G‐6‐PD. The kinetic study revealed two distinct populations of erythrocytes that were nearly equal in number. One cell population showed reduction rates between 0 and 25% of normal, whereas the second cell population displayed rates within the range seen for normal cells. Single‐cell indices of cell size, cell hemoglobin content, and ratio of cell hemoglobin to cell size did not correlate with single‐cell reduction rates and were not significantly different between the two populations. These results provide quantitative support for the X‐inactivation hypothesis i

ISSN:0361-8609    

DOI:10.1002/ajh.2830230402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractAlthough large vessel thrombi are occasionally reported in patients with homozygous sickle cell disease, the role of intravascular coagulation in typical pain crises is controversial. Therefore, we studied 24 sickle cell patients during and between episodes of pain crisis, using several sensitive tests of hemostasis. Fibrinogen was measured by a clotting assay, β3‐thromboglobulin (β‐TG) and fibrinopeptide A (FPA) were quantitated by radioimmunoassay, and protein C was determined by absorbing the zymogen from test plasma, activating it with thrombin‐thrombomodulin complex, and measuring activity with a selective synthetic substrate. Fibrinogen was elevated in asymptomatic patients (355 ± 145 mg/dl) but was no different from the value in these same patients during crisis (333 ± 180 mg/dl, p>0.1). Similarly, β‐TG 136 ± 52 ng/ml vs 118 ± 56; FPA 3.7 ± 4.8 ng/ml vs 5.2 ± 4.5, and protein C 71 ± 20% vs 66 ± 19 showed no important changes during crisis. However, all these values were significantly different from those in age‐ and sex‐matched healthy controls. (β‐TG, fibrinogen, and FPA were elevated (p<0.001, 0.005, and 0.05, respectively), and protein C was decreased (p<0.003). We conclude that while chronic intravascular coagulation is common in patients with sickle cell disease, there is no evidence that the pain crisis per

ISSN:0361-8609    

DOI:10.1002/ajh.2830230403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThirteen subjects 5‐20 years of age with the chronic, autoimmune form of idiopathic thrombocytopenic purpura (ITP) were given intravenous gammaglobulin (Gamimune; Cutter Biological, Berkeley, CA) in a dose of 400 mg/kg per day for 5 consecutive days. Two of the 13 children had undergone splenectomy; the other 11 had not. Eight of these 13 children had also received corticosteroid therapy with no sustained increase in platelet of counts. Six of 13 children had a good or excellent response to the first 5 day course of gammaglobulin therapy, and one had a fair response. The peak platelet count occured within 7 days of the start of therapy except in one patient, whose platelet count peaked on day 12. Six of seven patients who initially responded to Gamimune required booster doses to maintain platelet counts at a safe level. All children had marked increases in serum IgG following Gamimune except one (who had undergone splenectomy for chronic ITP), who had high baseline levels of immunoglobulin G (IgG). No untoward reactions necessitating cessation of therapy were encountered during this study. The most common side effect observed was headache. During the first year of follow‐up after Gamimune, three of seven initial responders became refractory to Gamimune therapy. Two of these three refractory subjects later underwent splenectomy with excellent response. The third refractory patient who was splenectomized prior to gammaglobulin therapy had spontaneous remission of his ITP 5 months after the last dose of Gamimune. Three of the four other initial responders have continued to do well and have maintained platelet counts above 40,000/mm3(one without booster). The fourth subject dropped out of the study. Thus our observations indicate that Gamimune is an effective form of treatment for some children with chronic ITP, and can be considered as an alternative to splenectomy or as a potential therapeutic modality in those who have failed to respond to splenect

ISSN:0361-8609    

DOI:10.1002/ajh.2830230404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractWe evaluated the outcome of seven severe hemophilic patients who underwent four total hip and four total knee arthroplasties since 1976. These patients have been followed at regular intervals over a period of 2.5–9.5 years (mean 5.8). Of the four total hip replacements, one had to be removed because of loosening and secondary infection 3 years after the initial surgery but was salvaged by pseudoarthrosis; the other three are pain‐free and radiologically stable and have an excellent range of motion 2.5, 5, and 7 years postoperatively. Of the four total knee replacements, one had to be removed because of infection but was successfully salvaged by arthrodesis; one patient has loose components, but the prosthesis is still functional; and the final patient with bilateral knee prostheses is pain‐free with limited but functional range of motion. Clotting‐factor replacement therapy was effective in controlling intraoperative bleeding, even in a patient with an inhibitor, and only one procedure was complicated by hematoma formation. We conclude that prosthetic joint replacement may be safely performed in hemophilic patients but should be reserved for those who have limited function because of severe pain, joint destruction, and deformity. Total hip arthroplasty is as successful in these patients as in nonhemophiliacs. Total knee arthroplasty provides relief of pain, reduces the frequency of hemarthroses, and corrects most of the deformity, but it is usually associated with a limited range of

ISSN:0361-8609    

DOI:10.1002/ajh.2830230405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractOne‐hundred thirteen adults and children with hemophilia or other congenital bleeding disorders were vaccinated against the hepatitis B virus. Each patient was given three subcutaneous injections of the vaccine at monthly intervals and then a fourth booster dose 14 months after the first. The vaccine was highly immunogenic, since 111 of 113 patients (98%) produced anti‐HBs (10 mlU/ml or more). After the first three vaccine doses and after the booster dose, ten anti‐LAV/HTLV‐III‐positive hemophiliacs produced anti‐HBs but had a lower average titer than anti‐LAV/HTLV‐III‐negative hemophiliacs. Of the 23 patients treated with concentrates in the 15 month postvaccination period only, none acquired HBV infection. Of the 50 patients treated with concentrates also in the 6 month prevaccination period, one developed hepatitis B. In summary, the vaccine was highly immunogenic in both children and adults with hemophilia; anti‐LAV/HTLV‐III‐positive patients responded to the vaccine, but the average anti‐HBs response was lower; no case of hepatitis B occurred in patients treated with concentrates only in t

ISSN:0361-8609    

DOI:10.1002/ajh.2830230406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe prognosis and optimal management of patients with thrombotic thrombocytopenic purpura (TTP) who fail initial therapy with plasmapheresis or splenectomy are unclear. We report our experience with eight patients with TTP who did not respond to initial therapy. Seven patients achieved complete remission when alternate therapy was started soon after the recognition of initial treatment failure. One patient who received no alternative therapy died of progressive TTP. Our cases combined with those in the literature indicate a 74% salvage rate for patients who fail initial treatment for TTP. The combination of splenectomy, dextran, and steroids appears to be an effective treatment for patients with TTP who fail to respond adequately to plasmapheresis.

ISSN:0361-8609    

DOI:10.1002/ajh.2830230407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractPure red cell aplasia (PRCA) results from the failure of erythrocyte differentiation and may respond to immunosuppressive therapies. We have treated nine patients with PRCA refractory to steroids and/or cyclophosphamide with anti‐thymocyte globulin (ATG). Six patients had normal numbers of erythroid bursts (from erythroid burstforming units) or erythroid colonies (from erythroid colony‐forming units) detectable in vitro, and all responded to therapy with ATG. In vitro studies suggested T‐cell inhibition of erythropoiesis in four of these six patients and humorally mediated erythroid suppression in one. In three individuals, virtually no erythroid progenitors were detected in marrow culture. None of these patients responded to ATG. Myelo‐fibrosis, 5q‐ chromosomal abnormality, or the subsequent development of thrombo‐cytopenia in these individuals suggested that PRCA resulted from an intrinsic stem cell disorder. Our studies demonstrate that ATG is effective therapy for PRCA, and it may be especially useful in children or other patients in whom alkylating agents are not appropriate. We also confirm that erythroid growth in marrow culture predicts those patients who will respond to ATG or other immunosuppressiv

ISSN:0361-8609    

DOI:10.1002/ajh.2830230408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractTwenty‐one unselected patients with refractory chronic anemias of various etiologies were treated with danazol, a synthetic attenuated androgen. All had previously failed treatment with hematinics, androgens, corticosteroids, high‐dose intravenous immunoglobulin, antithymocyte globulin, cytotoxic immunosuppressive agents, and/or plasmapheresis. Three patients with pure red cell aplasia and one with aplastic anemia responded. No responses were observed in 11 patients with myelodysplastic syndromes, two patients with myelofibrosis, and two with paroxysmal nocturnal hemoglobinuria. Remission in pure red cell aplasia was maintained with danazol alone in one patient and required combined low‐dose prednisone in two. Objective responses occurred in 2 to 3 weeks and therapy generally was well tolerated. To date, one patient with pure red cell aplasia remains in complete remission at 9 months on lowdose danazol alone. We conclude that danazol alone or combined with prednisone may induce and maintain remission in severe refractory pure red cell aplasia and possibly other chronic cytopenias characterized by immunologic marrow suppression. Further trials of danazol in treating these disorders are indi

ISSN:0361-8609    

DOI:10.1002/ajh.2830230409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractTwo patients from two separate families were diagnosed as having type IIB von Willebrand disease, because they had lifelong bleeding tendencies, prolonged bleeding times, no large von Willebrand factor multimers, and low levels of ristocetin cofactor in plasma with heightened ristocetin‐induced platelet aggregation. There was no history of bleeding, and no laboratory abnormalities were found in the parents and sibship of either propositi, in contrast with the autosomal dominant pattern of inheritance usually observed in type IIB von Willebrand disease. Abnormalities of ristocetin‐induced von Willebrand factor‐platelet interactions were less severe than in a patient from a previously reported family with type IIB von Willebrand disease studied in parallel. The peculiar features of these cases provide additional evidence of the existence of heterogeneity within this va

ISSN:0361-8609    

DOI:10.1002/ajh.2830230410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractA patient with hypothyroidism had ingested aspirin and bled profusely following dental extraction. The only abnormalities noted on coagulation survey were a prolonged aspirin bleeding time and reduced retention of platelets on glass beads. Based on this index case, an additional 12 hypothyroid patients, on no medications, were evaluated for a mild bleeding disorder, including studies with aspirin challenge. The results indicate that thrombin‐induced platelet serotonin release, following aspirin ingestion, was subnormal in most hypothyroid patients. However, only hypothyroid individuals with TSH levels of>60 μ U/ml have an increased hemostatic sensitivity to aspirin, as measured by the bleeding time test. These findings did not appear to result from decreased synthesis of the factor VIII‐von Willebrand factor complex. As this drug is commonly ingested, the effects of aspirin on bleeding may explain the easy bruising and menorrhagia that occur in hypothyroid individ

ISSN:0361-8609    

DOI:10.1002/ajh.2830230411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY