Liver disease in haemophiliacs.
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Chronic Disease↗
Biomedical subjects
U Hasiba
Publications and source records attributed to U Hasiba.
Asymptomatic structural liver disease in hemophilia.
In a study of persistent abnormalities of liver-function tests in hemophilic patients deficient in factor VIII or IX and treated with factor VIII or IX concentrates, we examined 14 liver biopsies from 13 anti-HBs-positive patients. None had any symptoms of liver disease. All had chronically abnormal levels of alanine aminotransferase. Histologic studies showed chronic persistent hepatitis in eight patients, chronic active hepatitis in four and fatty infiltration with portal fibrosis in one. Indirect immunofluorescence of antiserums containing anti-HBs or anti-HBc (or both) revealed nuclear and cytoplasmic fluorescence in the hepatocytes of eight of 12 patients. Specificity testing of these antiserums confirmed that hepatitis B viral markers are present in the hepatocytes of these anti-HBs-positive patients. These histologic derangements are probably related to frequent treatment with blood products obtained from multiple donors and to the persistance of hepatitis B virus in hepatocytes despite the presence of circulating anti-HBs.
Biopsy↗
Antithrombin Pittsburgh: an alpha1-antitrypsin variant causing hemorrhagic disease.
A 10-year-old boy had a severe lifelong hemorrhagic disorder that had necessitated more than 50 hospitalizations. Laboratory examination showed prolonged bleeding, clotting, partial thromboplastin, prothrombin, and thrombin times. These findings were due to a potent inhibitor of the thrombin-fibrinogen reaction. This inhibitor was similar to heparin in that it acted immediately and did not interfere with the coagulant activities of certain venoms. It differed from heparin in not being adsorbed to barium citrate or neutralized by protamine sulfate. The inhibitory effect was found in the alpha1-globulin fraction. It was identified immunologically and functionally as a double-banded alpha1-antitrypsin of a previously unreported phenotype. The inhibitory effects were depressed by trypsin and heterologous anti-alpha1-antitrypsin.
Antithrombins↗
Chronic hepatitis in hemophilia.
The relationship of chronic hepatitis B and/or liver dysfunction to treatment in 113 hemophiliacs was evaluated by the enzyme tests, SGOT and SGPT, and by the presence of circulating hepatis B surface antigen (HbsAg) or antibody (anti-Hbs). The hemophiliacs were divided into three groups according to treatment pattern. Individuals who had received multiple doses of plasma fractions, derived from four or more commercial lots were placed in tgroup I "large Exposure". Group II "Small Exposure" had been treated with fractions from three or fewer lots and Group III "Cryo" had never received commercial fractions, but had been treated with cryoprecipitate. Abnormal liver function tests (LFT's) were found in 87% of Group I and 76% of Group II, but in only 16% of the "Cryo" group. Differences in LFT's were not great between treated VIII and IX deficient patients. All patients treated with 100,000 units or more showed either persistent or intermittent abnormalities. In the high exposure group, this history of past, overt hepatitis had no influence on observed LFT's. The sera of all patients in the high exposure and all, except one, in the low exposure groups were positive for HbsAg or anti-Hbs by RIA. Splenomegaly was found in 13% of fraction-treated patients. We conclude that there is biochemical evidence of liver disease following large exposure to commercial VIII or IX fractions, which should temper the physician's decision to start treatment with these fractions. On the other hand, evidence that their continued use produces mounting liver dysfunction is insufficient to withdraw this very effective and life-changing treatment from these individuals.
Alanine Transaminase↗
Letter: Death in hemophiliacs.
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Age Factors↗
Treatment of amyloidosis associated factor X deficiency.
This is the tenth patient in thirteen years to be reported with the findings of an isolated factor X deficiency associated with primary amyloidosis. A favorable response to factor IX concentrate was manifested by temporary clinical and laboratory correction of her diathesis. This mode of treatment, therefore, provides an approach to therapy for bleeding complications in this group of patients who have previously failed to response to fresh frozen plasma.
Amyloidosis↗
Splenunculectomy in recurrent thrombocytopenia.
A 13-year-old boy developed thrombocytopenic purpura in 1953 which improved during 4 weeks of cortisone therapy. Following 13 years of intermittent symptoms the platelet count was found to be 8,000/mul. After splenectomy the patient was asymptomatic for 8 years, but had a recurrence of symptoms and thrombocytopenia in 1974. An initial spleen scan with 99Tcm sulfur colloid was negative; but when repeated with a gamma-camera and shielded liver, a splenunculus was demonstrated. After splenunculectomy a rapid remission occurred, and the patient has been well for 13 months.
Adolescent↗
Marginal neutrophil pool size in normal subjects and neutropenic patients as measured by epinephrine infusion.
The marginal granulocyte pool (MGP) was measured by epinephrine infusion in normal and neutropenic subjects. Neutrophil response curves to doses of 0.025 to 0.3 mg. in three normal subjects indicated that maximal neutrophil response was achieved by 0.1 mg. In 21 normal subjects, absolute neutrophils increased from 700 to 3,100 per microliter. The percentage increase ranged from 18 to 107 per cent of baseline. The per cent increase tended to be greater with low-normal baseline neutrophils than with high-normal neutrophils, although this relationship was not observed when increase was determined in absolute values. In neutropenic patients mean per cent increase of neutrophils was greater than observed in normal subjects, 121 vs. 50 per cent. Although the increase expressed in absolute neutrophil numbers was less in subjects with lower baseline neutrophil concentrations, there was an inverse correlation between the baseline neutrophil concentrations, there was an inverse correlation between the baseline neutrophils and the per cent increment following epinephrine. Mean increase was 200 per cent in patients with less than 200 neutrophils per microliter, compared with 61 per cent in patients with 1,000 to 1,500 neutrophils per microliter. These results indicate that circulating granulocyte pool (CGP) size may be misleading with respect to total blood neutrophils and in a sense confirm the concept of shift neutropenia, a decreased CGP and MGP as neutropenia becomes more profound suggests that shift neutropenia may be a normal physiologic methanism rather than a distinct neutropenic syndrome.
Adult↗
DiC-like syndrome after envenomation by the snake, Crotalus horridus horridus.
After envenomation by the timber rattlesnake (Crotalus horridus horridus) a young man showed massive swelling and ecchymoses of the involved extremity, generalized petechiae and a large hematoma of the left upper eyelid. Two weeks later he was completely well. The first blood sample was incoagulable and showed high titers of fibrin split products by the MISFI and staphylococcal clumping tests. Immounoelectrophoresis showed both D and E fragments, but only D was present at 18 hours. The profound thrombocytopenia and hypofibrinogenemia gradually improved, and split products disappeared. In vitro the venom had thrombin-like activity, clotting fibrinogen or plasma and aggregating platelets. These activities could be inhibited by antivenom but not by heparin. There was no evidence that thrombin formation was actually involved: hence, the syndrome is called DIC-like.
Adult↗
Water-insoluble paraproteins with anticoagulant properties.
A 78-year-old woman, who had received steroid therapy for four years, had strikingly prolonged prothrombin time (PT) and partial thromboplastin time (PTT). The presumptive diagnosis was chronic hemolytic anemia. Platelet count and functions, fibrinogen, and factor XIII assays were all normal, but other factors assayed abnormally low; Sia water-dilution test was positive. When water-insoluble protein was removed by centrifugation, coagulation factors became normal. Dissolution of this precipitate in normal plasma caused marked prolongation of PT and PTT and lower factor assays. Serum electrophoresis showed a homogeneous M spike and an anomalous IgM, lambda-antigenic type in the gamma-globulin zone at point of origin. Ultracentrifugation of serum and of the precipitate showed 10% S17 and almost 100% S17 components, respectively. Five other patients with water-insoluble paraproteins were tested; two were clot-inhibitory.
Aged↗
Home treatment for hemophilia.
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Adolescent↗
Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies.
The hypothalamic-pituitary-gonadal axis was evaluated in two groups of age-matched men with documented biochemical and histologic liver disease and compared to that of age-matched normal controls. Basal testosterone levels (p less than 0.05), spermatozoa concentrations (p less than 0.01), and seminal plasma volume (p less than 0.01) were reduced in the alcoholics studied with liver disease, but not the hemophiliacs with liver disease when compared to the normal controls. No difference in estradiol levels was noted between groups. Basal follicle-stimulating hormone and luteinizing hormone (LH) concentrations were increased (both p less than 0.01) in the alcoholics while only LH concentrations were increased (p less than 0.01) in the hemophiliacs compared to the normal controls. Gonadotropins (follicle-stimulating hormone and LH) and testosterone responses to clomiphene and to luteinizing hormone-releasing factor (LH only) in the alcoholic population studied, further distinguished the alcoholics from the hemophiliacs and the normal controls. The basal levels of the other anterior pituitary hormones (growth hormone and thyroid-stimulating hormone) as well as their provocative responses to thyrotropin-releasing hormone also distinguished the alcoholics from the hemophiliac population. Based upon these results, we propose that factors other than the liver disease per se are responsible for the disturbances of hypothalamic-pituitary-gonadal function observed in men with biochemically as well as histologically advanced stable liver disease.
Adult↗
Prekallikrein (Fletcher factor) deficiency in clinical disease states.
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Blood Coagulation Disorders↗
Changes in coagulation factors, complement, immunoglobulins, and immune complex concentrations with plasma exchange.
Seventeen patients with a spectrum of immunologically-related disorders were studied before and immediately after plasma exchange (PE) for changes in coagulation factors, complement, immunoglobulins, and immune complex levels. Each PE replaced 50 per cent of the plasma volume with 5% albumin and saline. With PE, coagulation profiles indicated a decrease of 23 to 55 per cent in the levels of fibrinogen, Factors II, V, VII, VIII, IX, X, XI, XII, and Fletcher factor. Only minimal changes were noted in the prothrombin time and activated partial thromboplastin time. Most coagulation factors, except fibrinogen, returned to baseline by 48 hours. Following three PE/week, fibrinogen was reduced by 51 per cent; other factors were not significantly altered. C3 and C4 fell by 35 to 40 per cent with each PE; these approached baseline by 24 hours. Immunoglobulins (G,A,M) were reduced by 34 +/- 3,37 +/- 3 and 34 +/- 3 per cent, respectively. After three PE, the total immunoglobulins were decreased by 50 to 55 per cent. Five of eight patients who had three or more PE developed hypogammaglobulinemia (IgG less than 450 mg/dl). Immune complexes were reduced by 50 +/- 4 per cent with each PE. Multiple exchanges in five patients led to a greater reduction (80 +/- 6%). Thus PE was an effective means of reducing immune complexes but led to hypogammaglobulinemia and hypofibrinogenemia.
Antigen-Antibody Complex↗
Prepooled cryoprecipitate for treatment of hemophilia A.
Lyophilized factor VIII concentrates, because of their convenience, are the most commonly used products for providing antihemophilic factor to patients with hemophilia A. Heightened concerns about associated complications indicate that cryoprecipitate usage will increase in the immediate future. We present a protocol for making cryoprecipitate more usable by "prepooling" individual units of cryoprecipitate in an "open" system. Our experience indicates this approach is safe, effective and acceptable to patients, including those on home therapy programs.
Factor VIII↗