bluuebunny/crossref_metadata_2025 huggingface dataset:
Heparin’s Endogenous Function, Primarily Anticeijxolar-Destructive, Incidentally Anticoagulant, is Dose, Source, and PH Related
Authors: Saliba M.J.
Published: May 2019

Heparin’s obscure endogenous function may be resolved by new experimental findings, reported by Saliba and coworker since 1963, with heparin use in controlled animal studies and patients with thermal burns and myocardial ischemia. Large doses of intestinal source heparin, administered topically and parenterally, significantly reduced burn extension, edema, fasciectcmies, parenteral fluids, skin grafts, and contractures. Then, similar large doses of intestinal source heparin significantly reduced the cellular-destructive pathophysiology of myocardial ischemia, improved electrocardiographic S-T segments 84%, reduced myocardial necrosis 32%, and salvaged creatine Phosphokinase 15%. Lung source heparin produced significant but lesser effects on S-T segment elevations and adenosine triphosphate levels. The large heparin dose needs, without bleeding problems, suggested more than anticoagulation was involved. Ml known heparin effects were theoretical mechanisms: anticoagulant, antithrombosis, antilipemia, antihistamine, anti-serotonin, antiproteolytic enzyme, anticcmplement, antilysosomal enzyme, and antiexcess positive ion. For those effects, individually often and collectively always, large doses of heparin were required. Inactivation-combination reactions of heparin with histamrine, serotonin and some tested proteolytic enzymes were ph related, acidic ph dependent, alkaline ph reversible. So, thermal burns and myocardial infarcts were two severe cellular-destructive diseases, with ischemic components, that were significantly improved by appropriately large doses of source specific heparin. It is concluded that at acidic phs intestinal heparin in larger than anticoagulative dose is mainly an anticellular-destructive agent, incidentally anticoagulant. New uses may result.
Change on Blood Coagulation, Platelet Function and Fibrinolysis in Diabetes Mellitus - Preliminary Report
Authors: Giustolisi R. , Musso R. , Lombardo T. , Russoand M. , Cacciola E.
Published: May 2019

Some coagulation aspects are studied in diabetes mellitus because this dismetabo-lic disease represents a “high risk factor” of predisposition leading to classical lesions of the vascular wall and thrombosis. Were studied 24 diabetic patients between 16 and 68 years old and 14 healthy subjects. Tests performed are followed: partial thromboplastyn time(PTT), plasma coagulation time RVV(RVV-T), antithrombin III(At-III), alpha2macroglobulin(a2M), fibrin/fibrinogen degradation products(FDP), ethanol gelation(EG) and protamine sulphate(PS), euglobulin lysis time(ELT), platelet adhesiveness to glass(PAG), platelet adhesiveness in vivo (PAV), platelet factor-3 availability(PF-3), platelet aggregation by ristocetin 1, 2-1, 5-1, 8 mg/ml(RIPA),

Diabetics showed a fall in At-III, increase a2M, a significant decrease ELT and increase FDP with often positivity EG. We also noted a shortening of PTT, PF-3 rate and RVV-T. In vitro platelets adhesiveness rises more than it does in vivo. Besides the PPP from diabetics increased the control subjects PAG. The RIPA is increased. Our findings showed, therefore, in diabetic patients a thrombophilic pattern by blood hypercoagulability and fibrinolytic activity decreased.
Marathon Run: Effects on Blood Coagulation, Fibrinolysis and Platelet Aggregation
Authors: Mandalaki T. , Dessypris A. , Louizou C. , Dimitriadou C. , Panayotopoulou C.
Published: May 2019

Blood coagulation, fibrinolysis and platelet aggregation were assessed in Finnishamateur Marathon runners, aged 30 to 57 in 1975 and 1976. After the run the mean valuesof aPTT showed a very significant shortening, prothrombin time and fibrinogen were not altered, euglobulin lysis time were significantly shorter, F.D.P. increased highly significantly. Protamine sulphate precipitation test became strongly positive, whereas ethanol gelation test and cryofibrinogen remained negative. Identical changes of the above parameters wereobtained both in 1975 and 1976. The mean values of platelet count showed a very significant rise in 1975 but not in 1976. A highly significant increase was noted for both the intensity and velocity of platelet aggregation induced by ADP and collagen in 1975. However in 1976this increase was not observed in all runners. The difference in response could be attributed to the environmental temperature factor (1975 :25°c-sunny, 1976 :18°C-cloudy). Also in 1976 the running time of the group was shorter than in 1975. Data on Cortisol levels are also given.
The Effect of Linolenoyl Sorbitol on Platelet Aggregation
Authors: Nathan I. , Dvilansky A. , Livne A.
Published: May 2019

The polyol ester of linolenic acid -Linolenoyl Sorbitol (L.S.), a synthetic lipid has marked affinity to membranes due to its hydrophobic long chain fatty acid and its hydrophilic region,, Dual effect on washed human platelets was demonstrated by L.S. Preincubation for one minute of L.S. with washed human platelets at 10-7 to 10-5 potentiated aggregation induced by ADP. Preincubation of L.S, either at higher concentrations or for a prolonged time diminished platelet aggregation. Methyl ester of linolenic acid had no potentiation effect on platelet aggregation, but attenuated aggregation similarly to linolenic acid when used in the same concentration as L, S. Thrombin induced aggregation of human platelets was affected similarly by L.S. Increased release of !4<G labeled serotonin occurred concomitantly. Prior preincubation of platelets with L.S.; 10−6M - 10−5M increased acetylcholine esterase activity. The increase in enzyme activity was not affected by prolonging incubation time. However, linolenic acid per se inhibited acetylcholine esterase activity. These results indicate that the effect of L.S. on platelet membrane acetylcholine esterase activity does not correlate with its effect on platelet aggregation.
Qualitative Platelet Abnormality due to Absence of Adp-Adrenal I Ne-Induced Release Reaction
Authors: Ciavarella N. , Mitrio V. De , Coviello M. , Scaraggi A. , Schiavoni M.
Published: May 2019

We present a 14 y. old male patient with a history of bleeding tendency characterized by frequent epistaxis and easy bruising. The template Ivy bleeding time was prolonged (>15′, 15′, 12′). Platelet (P.) retention was reduced (0%, 15% 20%). P. aggregation induced by collagen was normal but second-phase aggregation induced by ADP and Adrenaline (ADR) was absent. Ristocetin-induced aggregation was normal. Platelet ATP, ADP and 5-Hydroxytryptamine (5 HT) content were normal.

C-5HT uptake was also normal. When incubation of PRP withC-5HT was continued up to 5hr,radioactivity was retained within the P. as in controls.C-5HT release was normal when induced by collagen but strongly reduced by ADP and ADR. Ma Iondia Idehyde production by P. during secondary aggregation was normal. These data are sufficient to rule out a Storage-poo I-disease or an ASA-1 ike-syndrome. Moreover the mother and the brother of the patient have also a mild hemorrhagic diathesis and some similar laboratory abnormalities. This rare condition is op-posite of a P. abnormality characterized by inability of P. to respond to collagen, reported by Hirsh et al., Papayannis et al. and Mielke et a I.. This may give a new insightinto the phisiology of P. aggregation.
Determination of Sh-Groups of the Platelet Membrane
Authors: Stoltz J.F. , Nicolas A.
Published: May 2019

The authors have determind the SH group (P-SH) of the platelet membrane using four different methods (spectrometric dosage, radio isotopic count, atomic absorptoon and liquid phase, electrophoresis).

This work was supported by DRME (grant 76.34.146.00.480.75.01)
Increased Platelet Aggregation due to a Plasmatic Aggregating Activity
Authors: Serneri G.G. Neri , Abbate R. , Gensini G.F. , Favilla S. , Mugnaini C.
Published: May 2019

In various clinical states an increased platelet aggregation has been observed, but its mechanism(s) is not yet completely understood. Plasma of some patients with history of myocardial infarction (MIP) or with cerebrovascular disorders (CVP) delays platelet disaggregation after aggregation by ADP (Neri Serneri et al 1974) and induces morphological changes in control platelets (Schatz and Gross 1975). In a group of 27 MIP and 20 CVP we identified 16 MIP and 12 CVP with plasmatic aggregating activity (AA) by cross-matches in a modification of the method of Wu and Hoak (1974) for platelet aggregates. As the AA disappeared after heparin treatment (12,500 U × 2 for 7 days) we investigated whether the AA was related to an activation of clotting processes. At this purpose we measured in these patients and in those without AA the concentration of high molecular weight fibrinogen complexes (HMWFC) by agarose 4% gel-filtration. The patients with AA showed a significantly (P<0.0l) higher HMWFC concentration (9.68±2.15 %) than those without AA (5.41±1.7 %) but the AA was not related to the HMWFC themselves, which on the contrary showed a mild antiaggregating activity. On gel-chromatography of the whole plasma the AA was eluted at an elution volume at which factor X is usually collected.
Plasmin Inhibitors in Human Urine
Authors: Sumi H. , Takada Y. , Takada A.
Published: May 2019

By the gel filtration of urinary protein on Sephadex G-200, two peaks of activity to hydrolyze Nα-acetylglycyl-L-lysine methyl ester (AGLMe) were detected. One was the native form of urokinase, and the molecular weight was about 54,000. The other was of high molecular weight, and eluted in void fraction. The high molecular form was thought to be a complex of urokinase and urinary plasmin inhibitor (UPI). By using Arg-Sepharose, membrane filter (M.W. 10,000), and pevikon block electrophoresis, we could isolate four types of UPI from normal human urine. One UPI was positively charged at pH 8.6, and of high molecular weight. Other types were negatively charged, and the molecular weights by gel filtration on Sephadex G-200 were about 67,000 (UPI6.7), 45,000 (UPI4.5), and 22, 000 (UPI2.2), respectively. In acrylamide disc gel electrophoresis, UPI57 migrated to serum prealbumin fraction, and UPI45 and UPI? 2 were less anionic. Negative-charged UPIs could be adsorbed on trypsin-Sepharose, and were thought to be identical to urinary trypsin inhibitors. Purified UPIs showed strong inhibition on caseinolytic- and esterolytic-activities of plasmin, and the total activity was about 16 UPIU(inhibited 16 casein U of plasmin)/liter of urine.
Inhibition of the Platelet Release Reaction in Vivo by Sulphinpyrazone and Metabolites
Authors: White A.M. , Butler K.D.
Published: May 2019

One of the earliest responses in the Arthus reaction to the injection of antigen is a transient thrombocytopenia which reaches a maximum in 15-30 min. This response is apparently associated with the platelet release reaction since it is inhibited by sulphinpyrazone, aspirin, phenylbutazone and indo-methacin but not dipyridamole or heparin. It has now been shown that two human metabolites of sulphinpyrazone namely p-hydroxysulphinpyrazone and the sulphone of sulphinpyrazone are equipotent with the parent molecule in inhibiting the thrombocytopenia and by inference the platelet release reaction.

The relative potencies of drugs measured in this way differ markedly from their relative potencies towards collagen aggregation ex vivo. Thus sulphinpyrazone(50 mg/kg) given 1 h before challenge inhibits the thrombocytopenia by 79% but not collagen aggregation ex. vivo. Aspirin(10 mg/kg) showed about the same potency in vivo and ex vivo with 47% and 50% inhibition, respectively. Phenylbutazone was less active in vivo than ex vivo. These results again serve to demonstrate the effect of anti-coagulants, particularly citrate, on platelet reactivity towards drugs and emphasize the need for sound in vivo methods.
Antithrombin III Activity, Measured with a Chromogenic Substrate, in Patients with Hepatic Cirrhosis, with Prosthetic Heart Valves and During Parenteral Administration of Medroxyprogesterone Acetate as a Contraceptive Agent
Authors: Baele G. , Matthys E. , Cock G. De , Thiery M. , Barbier F.
Published: May 2019

Antithrombin III (AT III) activity was assayed on heat defibrinated plasma using a synthetic chromogenic substrate, benzoyl-Phe-Val-Arg-p. nitroanilide. AT III activity in 30 normal subjects averaged 95% ± 18 (± 1 SD). As AT III is synthesized in the liver, we measured its activity in 72 samples from 44 patients with hepatic cirrhosis. The mean activity (49% ± 23) was significantly lower than in the control group. AT III activity was also measured in 32 patients with prosthetic heart valves receiving sodium warfarin therapy. The mean activity in this group (90% ± 23) fell in the normal range. It also did not differ significantly from the mean activity (95% ± 29) in a similar (matched for sex and age) group of 32 subjects, also treated with sodium warfarin but for other reasons than bearing a prosthetic heart valve. As low AT III levels have been reported in women using a combined oral contraceptive, we also measured AT III in 19 women receiving trimonthly injections of 150 mg of medroxyprogesterone acetate as contraception. AT III levels in this group of women (102% ± 23) were found to be normal. So the oestrogen in the combined contraceptive may be responsible for the reported fall in serum AT III activity.
Circulating Platelet Aggregates and Increased Platelet Turnover in Hypertensive Patients
Authors: Abbate R. , Gensini G.F. , Marinoni M. , Lagi A.
Published: May 2019

Cerebrovascular disorders and particularly TIA, frequently due to circulating platelet aggregates, represent a most frequent complication of high blood pressure.28 patients affected by high blood pressure of different aetiology have been investigated for the presence of circulating platelet aggregates according to Wu and Hoak (1974). In 23 patients we observed circulating platelet aggregates unrelated to the aetiology of high blood pressure. These patients showed also an increased number of megathrombocytes (Garg et al. 1971) so indicating the probable formation of irreversible aggregates. These patients usually did not show a plasma aggregating activity investigated by Wu and Hoak method on cross-matches of patient’s PPP with control’s PRP. The appearance of circulating platelet aggregates is related to blood pressure values, and decreases after the blood pressure has returned to normal values and after anti-aggregating treatment.
Haemophilic Arthropathy - Ultrastructural and Microprobe Analysis
Authors: Duthie R.B. , Stein H.
Published: May 2019

Biopsy specimens of synovial membrane and of articular cartilage, from fifteen patients who had undergone various reconstructive procedures, were studied h istochemically, by transmission electron microscopy and by electron probe analysis. Synovitis was obvious with the presence of cells resembling fibroblasts but containing intracytoplasmic, electron dense particles, i.e., sideromes. However by electron microprobe analysis not all these electron dense particles contained iron and therefore cannot be considered as ‘true sideromes’. There appeared to be a quantitative relationship between the presence of true sideromes and the degeneration of both synovial cells as well as articular chondrocytes. Although orientation was difficult many chondrocytes in the superficial and middle zone layers had true sideromes in their cytoplasm. They showed advanced necrosis with fissuring and clefting of the matrix as well as chondrocyte clustering. Those not containing true sideromes, although abonormal, showed less advanced cellular changes. All B type synovial cells and chondrocytes also demonstrated a phagocytic propensity to iron degradation products.
Conditions Contributing to the Stability of Factor VIII Coagulant Activity
Authors: Exner T. , Rickard K.A. , Kronenberg H.
Published: May 2019

Factor VTII tends to become less stable the greater its degree of purification. The loss of factor VIII during preparation of high activity concentrates makes such processes uneconomical. Conditions contributing to the stability of factor VIII were investigated.

High purity factor VIII was incubated with plasma components fractionated by gel filtration and by anion exchange chromatography. Factor VIII activity was assessed initially and after several hours incubation. Several fractions destroying factor VIII activity were clearly resolved. Fractions stabilizing factor VIII were associated only with albumin.

Various buffer systems were investigated similarly. A non-chelating buffer system containing albumin was found to give optimal factor VIII stability.
Particulate Material in Factor VIII Concentrates
Authors: Eyster M. Elaine , Nau Martin E.
Published: May 2019

Particulate material in Factor VIII concentrates might be associated with reactions such as dizziness, visual disturbances and dyspnea following infusions.

Factor VIII concentrates from three different manufacturers were reconstituted and passed through an Ultrapore blood transfusion filter.(Pall Corporation, Biomedical Products Division, Glen Cove, L. I.). The screen was removed, fixed in glutaraldehyde, dehydrated, critical point dried in CO2, plated with gold paladium and examined in an AMR 900 scanning electron microscope. Photomicrographs at 200 to 2,000 × magnification revealed a large amount of non-cellular debris adherent to the screen which retained particles of greater than 40 μ. When this material which was partially soluble in citrate saline phosphate buffer pH 6.0 was eluted and tested by immunodiffusion using antisera to whole human sera, IgG and fibrinogen, two precipitin bands were apparent.

It is concluded that Factor VIII concentrates contain non-cellular particulate material which is retained by a 40 μ screen filter and which may be composed in part of fibrinoprotein. The clinical significance of this material is uncertain.
Convenient Microtiter assay for von Willebrand’s Factor
Authors: Weksler B.B. , Cheng T. , Ley C.
Published: May 2019

A simple method for measurement of von Willebrand’s factor (VWF) suitable for the clinical coagulation laboratory would substantially aid in the differential diagnosis of bleeding disorders We have developed a simple macroscopic titration assay of plasma VWF using the Ristocetin induced aggregation of washed, fixed normal platelets. The assay employs arithmetic dilutions of test plasma in buffer, Ristocetin and washed, fixed platelets in a final volume of 0.4 ml per well. After 20 minutes’ agitation on a rotary shaker at room temperature, an endpoint of visible aggregation can be determined. Fifty normal plasmas tested had a mean titer of 1/500 (range 1/240 to 1/853) whereas 8 plasmas from patients with known von Willebrand’s disease (VWD) had a mean titer of 1/21 (range 1/10 to 1/186). Deviation from the normal range correlated with the severity of the VWD. Reproducibility of results was within ±10%.

Platelets washed before fixation with paraformaldehyde (method modified from Allain et al, J. Lab. Clin. Med. 85:318, 1975) appear almost twice as sensitive to VWF in this assay as those fixed in platelet rich plasma and washed subsequently. Fresh and frozen plasmas give equivalent results, permitting storage of specimens. This microtiter assay thus offers a sensitive measure of VWF Ristocetin cofactor activity, utilizes stable and standardizable reagents, requires only small amounts of patient plasma (or other biological materials) and permits rapid testing of different specimens simultaneously.
Sinoviorthesis with AU-198 in 25 Cases of Hemophilic Arthropathy
Authors: Martin-Villar J. , Ortega F. , Magall M. , Gago J.
Published: May 2019

Sinoviorthesis with radioactive gold has been carried out on 25 joints of hemophilic patients with the object of evaluating the clinical results (lessening of the frequency of hemorrhagic accidents, functional improvement, etc.) in the joints treated.

Only Grade II and III joints (Palmer-Cotler) were injected. The doses of Au-198 injected varied according to patient’s age and joint. Adultes 9 knees with 4 mC, 5 elbows with 5 mC. 1 ankle with 2 mC. Childrent 7 knees with 5 mC, 2 ankles with 2 mC, 1 elbow with 2 mC. Recurrent hemarthrosis was the only criterion for treatment. These joints were re-evaluated after a period of no less than 6 months and no more than 16 months. The criteria for evaluation of results weret No Improvement (Nl); Slight Improvement (Si), by subjeotive appreciation; Good (G), with improvement in clinical signs and symptoms and lessening of hemarthrosis frequency; Very Good (VG), with good articular function, no sinovial hypertrophy, no new hemarthrosis and stable radiographic image. Results obtained were s Adultes VG 14%; G 5J%; SI 14%; NI 20%. Children s TG 50%; G 20%; SI 10%; NI 40%.

In conclusion, we believe that this therapy should be considered for the treatment of hemophilic arthropathy.
Radioactive Synoviorthesis in Haemophiliac Haemarthrosis
Authors: Fernandez-Palazzi F. , Boscho N.B.
Published: May 2019

Because haemarthrosis is the main musculoskeletal symptom in haemophilia, with bleeding originating from the synovial membrane, its prevention by either synovectomy, or better synoviorthesis, must be the principal aim of orthopaedic treatment,, Since 1976 we have treated 10 patients with recurrent haemarthrosis of joints (5 knees, 3 elbows and 2 ankles) with radioactive synoviorthesis with gold (AU 198), obtaining in all of them a diminution of frequency in bleeding episodes and factor VIII requirements, and in 7 a total absence of new haemarthrosis. Previous to the syno-viorthesis, a joint screening with Tecnesium was performed, in order to compare the inflamatory status of the synovia with that five months after synoviorthesis. The technique used as well as dosage of AU 198 and factor VIII coverage, Is presented.
A Case of Henoch-Schoenlein Purpura in Hemophilia
Authors: Gonzaga A.L. , Azevedo C.B. , Baré L.F.
Published: May 2019

A 25-year-old male, white, with severe hemophilia B (F.IX < 1%) developed a rash of small erythematous macules, purpuric spots and petechia on the lower extremities. These skin lesions were discrete, not pruritic, not papular and with no areas of necrosis. No relationship to previous infection was determined. As the patient did not present any other clinical alteration, he was observed daily on an ambulatory basis in a four days’ period, without any medication. On the fifth day parallel to the disappearance of the skin lesions, the patient began to complain of abdominal pain, in crisis of moderate intensity. As the abdominal discomfort increased rapidly on the following 24 hours, we introduced specific therapy on an in-patient basis. The case evolved to an acute abdominal picture that required surgical intervention. The laparathomy resulted in large ressections of jejunum and ileum that showed large hemmorrhagic and necrotic areas. The post-operative period elapsed without incidents and the patient left the hospital in three weeks. This case that at the beginning could not give us a clear diagnosis of an anaphylactoid purpura shows us once more that in hemophilia, we must transfuse as early as possible.
Psychological Studies in Hemophiliacs in a Summer Camp
Authors: Ripa T. , Scaraggi F. , Pasqual Marsettin E. , Dentico A. , Ciavarella N.
Published: May 2019

Hemophiliacs can show disturbed interpersonal adaptation expressed by hypersensitivity, anxiety aggressiveness and introversion. Our study has been carried out in a summer camp (Rosamarina - Puglia - Italy) during a period of 15 days on a group of 28 hemophiliacs in order to prove the existence of these psychological disorders and to establish a relationship with the following: A) Condition of patient-mother dependence; B) Socio-cultural standard of living of the patient’s family; C) Severe physical handicap of the patients; D) Type of treatment used on the patients (e.g.: home therapy and/or self treatment). Light psychological troubles were encountered in about 70% of the subjects which were correlated with A, B, C, D. The remaining subjects showed no trouble mainly because they had no severe physical handicap and could benefit by home therapy and/or self-treatment. In conclusion, we suggest that the psychological problems can be solved with psychological dispensary for the patient and his family and also offering the hemophiliacs maximum therapeutic resources (Home therapy and self-treatment).
Personality Characteristics of Adult Hemophiliacs
Authors: Charney D.S. , Caldwell A. , Ackerman L.L. , Strickler E.
Published: May 2019

The psychological characteristics of 36 adult hemophiliacs, mean age 29.1 years, were analyzed by means of the Minnesota Multiphasic Personality Inventory (MMPI).

The MMPI profile patterns were compared between various groups of the hemophiliac sample. By the clinical criterion used in our clinic, the sample was divided into severe and mild-moderate groups. The mild-moderate group appeared to be mildly anxious-hysterical, frightened, and health preoccupied with a profile of '317-2 9 5684 0/. The severe group appeared to be more estranged and alienated than the mild-moderate group, and has a significantly higher psychopathic deviate scale (P<.01). The mean profile of the severe group was '458 23-9167 0/.

The most striking differences were found in comparing subgroups of high (N=9) vs low bleeders (N=9) within the group of severe hemophiliacs with factor levels of 3% or less. The high bleeders (>243 units/lb/year, mean Factor VIII level 1.6%) were much more disturbed, had all mean clinical scales above 60 (8'25137496-0/) and significantly higher scores for Depression, Psychasthenia, and Schizophrenia (P <.05). The low bleeders (< 243 units/lb/year, mean Factor VIII level 1.8%) had no mean scale scores above 60 ('34519687 2/0).

The results indicated a clear difference in the psychological adjustment of the high and low bleeders to their illness. The high bleeders had a marked increase in self negativity i.e. a sense of being defective, of hopelessness and of pessimism. Surprisingly, the low bleeders has adjusted auite well to their serious vulnerability.
Psychological Aspects of Training for home Treatment in Hemophilia
Authors: Delord S. , Allain J.P.
Published: May 2019

Training for home treatment has profound psychological implications. This study was undertaken to determine the optimal time in the hemophilic child’s development to begin this training. Nineteen preadolescents and 31 adolescents were trained during short weekly sessions and followed for a year. They also had interviews with a psychologist. During this one year period, parents of both groups were invited to participate in information sessions including technical training and informal discussions. Eleven of 12 preadolescents whose parents participated were successful in self-treatment whereas only 1 of 7 whose parents did not participate succeeded. Even when parents were not actively present during the training period, the adolescents had a success rate of 75%. In both groups, a positive psychotherapeutic effect was observed but since preadolescent were more flexible, an organizing psychological process was induced which involved both their approach to the disease and the child-parent relationship. The parents benefited from the information program, relieving their anxiety and gaining a better intellectual and gemotional approach to hemophilia. Although the adolescents were highly successful, it is suggested that the training be started during preadolescence with active help from the parents. Then, maximum benefit and success rate would be expected.
School Attendance Pre and Post Home Infusion Therapy
Authors: Hummel L.
Published: May 2019

To compare the relationship between home infusion therapy and school attendance, 21 official school records of hemophilic boys on home infusion therapy were analyzed. The records show a mean absence of 40.4 days for one year pre and 25.3 days post home infusion therapy. Data included 18 subjects with two year pre and post home infusion therapy records. These 18 subjects had a mean absence of 40.9 days for two years pre and 26.4 days for two years post home infusion therapy. Data indicate boys on home infusion therapy have better school attendance than they did before home infusion therapy. The length of time they were on home infusion therapy did not seem to be significant. The grades in which the children were studied was also not significant.
Home Therapy for Haemophilia in Norway: Effect on Transfusion Frequency and Absenteeism
Authors: Evensen S.A. , Thaule R. , Grøan K.
Published: May 2019

Twenty-seven patients with haemophilia A or B (factor level of 1% or less) have so far been instructed to administrate concentrates of the deficient factor (mean dose: 14 units/kg) in case of episodic, uncomplicated bleedings without prior consultation with a physican. Twenty-five patients(21 with haemophilia A and 4 with haemophilia B) are at present included in the program. They represent 19% of all patients with severe haemophilia in Norway and range in age between 7 and 45 years. For 15 patients data from one year on home therapy have been compared with data from the preceding year. There was 77% reduction in days lost from work. The number of infusions increased 22%. Use of factor VIII and IX increased 37% because the mean dose per bleed was 27% higher than the dose previously received by the patients. Liver function tests remained within normal limits for all but 2 patients receiving factor IX concentrates. None were HBAg positive, 4 turned HBAb positive. Home therapy is practical and safe and improves the quality of life considerably.
Hemostasis in the Oral Cavity
Authors: Tomic D.
Published: May 2019

Various factors and reasons can be responsible for acute, severe or protracted hemorrhages in the oral cavity. Hemostasis with conventional methods frequently poses a difficult, dangerous and involved problem. A special method is developed utilizing the chemical and physical properties of inorganic and organic compounds, and this is found to be efficient for rapid and safe hemostasis. It acts on the blood coagulation process by lowering the pH value of blood, as well as by its astringent and osmotic properties. Altogether, the result is hemostasis and favorable wound healing. With the use of bone cement, the initial clot is physically protected, thus contributing more to reliable hemostasis, particularly after dental extraction. The method used, that is, bone cement in combination with the developed hemostatic agent, can be used without additional treatment for severe primary, as well as secondary hemorrhages. Patients suffering from hemophilia and other disorders of blood coagulation were treated successfully.
Hemophilia: A Moral Dilemma
Authors: VanHarlingen David
Published: May 2019

Hemophilia places stresses of a financial, social and psychological nature on both the victim’s family and the community. Decisions about having children, or paying for rehabilitative or preventive therapy with public funds, involve the resolution of value conflicts at a personal and at a societal level.

Moral/ethical dilemmas based on these and similar questions were constructed and administered to a group of non-hemophiliac classroom teachers. Our work indicates that these dilemmas are effective in presenting content knowledge about hemophilia problems and that they are able to increase one’s level of moral reasoning. This increases the probability that all possible consequences of an action will be carefully considered, although it does not lead automatically to a predetermined resolution of the dilemma.

The applicability of these dilemmas for use in genetic counseling of hemophilia families or to develop knowledge among parents and friends of new hemophiliacs will be explored.
Significance of Abnormal Liver Function Tests in Hemophiliacs: A Follow-Up Study
Authors: Mannucci P.M. , Ruggeri Z.M. , Capitanio A. , Pareti F.
Published: May 2019

It was previously shown (1) that hemophiliacs have a high incidence of abnormal liver function tests unaccompanied by clinical evidence of illness. Since single measurements are of little use to access the significance of such abnormalities and their possible relationship with chronic hepatitis, hemophiliacs with abnormal liver function tests were regularly followed with measurements carried out at least once a year. 20 patients with raised SGOT-SGPT were followed for up to 3 years; in 9, the abnormalities persisted throughout the whole observation period, whereas in 2 the enzymes were occasionally increased and in 9 they were always normal since the initial abnormal measurement. Out of 39 patients with increased serum gamma-globulins, abnormal values were 1 persistently observed in 11 followed for 3 years. In 28 patients followed for 2 years, persistently abnormal values were found in 21, whereas in 7 normal values were invariably found since the initial abnormal measurement. These findings show that liver function tests are persistently abnormal in a number of patients; in these, biopsy should be considered in order to undertake suitable therapeutic measures.
Analysis of Bleeding Frequency in Hemophilia.
Authors: Lovrien E.W. , Underwood S. , Hammerling J. , Rivas M. , Elder J.
Published: May 2019

Patients receiving AHF by home infusion therapy completed a form at the time of each infusion which allowed an accurate appraisal of bleeding frequency by site. A simple data management system was used to analyze the pattern of bleeding in 86 patients who averaged 28 months on the program with an age range from 2 to 52 years. The mean age was 17.1 years. The number of bleeds divided by the number of months = bleed per month index (BMI). The composite BMI for all 86 patients = 4.765 with a total of 11,504 recorded bleeds. 20% occurred in the head and neck, chest and abdomen = 16.66%, buttock and G.U. = 11.65%, upper extremity = 22.02%, lower extremity = 26.37% and miscellaneous = 3.30%. Extremities accounted for 48.39%. The most common bleeding sight was the abdomen 14.7166%, 2nd = nose 12.03%, 3rd = R lower leg = 10.68%. In the upper extremity, 15.76% were right sided compared to 6.25% left; lower = 23.34% right, 3.03% left. The knees accounted for only 1.113% of all the bleeds. The highest BMI on a patient = 12.4 avg. bleeds per month over 4 years.

The patients were divided into age categories of 3 years. The highest BMI for R. lower leg was age 6-9; R. knee age 12-15; abdomen 15-18, but high in all age ranges. Urinary bleeding was highest in early childhood in 0-3, 3-6, 6-9, and 9-12 year olds. By careful observation of the BMI, the management of early bleeding to prevent deformity should be enhanced. A high BMI may be used to guide prophylactic infusion. This study has demonstrated that a simple data processing system is useful in directing infusion therapy to minimize deformity.
Head Trauma in Hemophilia: Value of Computer Tomography of The Brain in Localizing Multiple Hematomas
Authors: Green D. , Weinberg P. , Cerullo L. , McLone D.
Published: May 2019

A 20 year old man with classical hemophilia (Factor VIII, 3%) was found unconscious in an alley after being struck on the head with a baseball bat. He transiently regained consciousness in the Emergency Room, but then became comatose and developed a right 3rd nerve palsy. He was immediately given AHF concentrate, 50 units per Kg, and had a computed tomographic (CT.) brain scan which revealed bilateral fronto-parietal subdural hematomas. These were removed through burr-holes and a right fronto-parieta1 craniotomy. He was maintained on 12-hourly doses of AHF concentrate, 50 u/per Kg, and did well for the first 3 post-operative days. Signs of increasing intracranial pressure then developed, and a repeat CT scan disclosed a right intracerebral hematoma. This was surgically evacuated and the remainder of his post-operative course was uneventful. He was discharged after 6 weeks of hospitalization with no residual neurological defect. A second patient, seen 6 years earlier for subdural hematomas following cranial trauma, also had evidence of deterioration in the early post-operative period. At that time, C.T. scans were not available, and the site of the new hematoma was not established. Although the patient recovered, there was a severe residual neurologic defect. Our experiences indicate that C.T. scans of the brain are valuable adjuncts in the management of head trauma in hemophilia, and, when combined with vigorous neurosurgical intervention, offer an improved prognosis.
Activated Prothrombin Concentrates in Management of Bleeding in a Classical Hemophiliac with Inhibitor
Authors: Whaun J.M. , Kaegi A.
Published: May 2019

Bleeding in hemophiliacs with circulating anticoagulants is still a serious management problem. We would like to report our efforts at achieving hemostasis in a 31 year old AHF deficient severe hemophiliac with inhibitor detected in Feb. 1972. He presented with right forearm flexor compartment bleed which did not respond to conservative management with Konyne (30 u/kg q3h) and necessitated a fasciotomy to relieve compression. No hemostasis occurred until 4 hrs. post-operatively when he received his first infusion of Auto-Factor IX*, 6 vials (60 u/kg). At this time he also received blood for his shocky state. With the institution of regular infusions of Auto-Factor IX alternating with Konyne, hemorrhage was controlled. A week later a split thickness skin graft (from R. thigh) was applied. With continued infusions of mainly Auto-Factor IX (60 u/kg q6h) the grafted and donor sites healed. The patient was subsequently discharged with full range of movement in all limbs. His inhibitor levels which ranged between 1 - 3 Bethesda units/ml shortly after admission over a period of 3 weeks rose to over 100 units/ml. Six months after the episode his inhibitor levels are still over 100 units/ml. Activated prothrombin concentrates are effective in hemostatic control of life-threatening bleeding in hemophiliac patients with inhibitors.

* Kindly supplied by Dr. Aaron Josephson, Travenol Laboratories, Chicago, 111. (Hyland Division).
The Management of two Cases of “Spontaneous” Factor VIII Inhibitors with high Dose Cyclophosphamide
Authors: Gomperts E.D.
Published: May 2019

Two patients with excessive bleeding associated with “spontaneous” Factor VIII inhibitors were studied. The first, a White male aged 52 years, was treated with high dosage cyclophosphamide and steroids together with plasmapheresis. An antigenic stimulus via concentrate and fresh plasma was given together with the stat dose of cyclophosphamide (1.6gm) together with prednisolone 60mg/day. Repeat plasmopheresis was carried out on two subsequent occasions shortly thereafter. The inhibitor level dropped progressively from 6.6 u/ml to almost unrecordable levels. However, escape from control was associated with the onset of hepatitis. Further therapy with an identical form of treatment failed to subsequently modify the inhibitor level which rose progressively to very high levels. In the second case, a White female aged 79 years, plasmapheresis was not carried out (inhibitor level 2.0 u/ml). Cyclophosphamide and prednisone were given in doses of 20 mg/Kg and 60 mg/day respectively. A Factor VIII antigenic load was given 24 hours before the cyclosphosphamide. Two subsequent cyclophosphamide pulses of similar dosage were given at approximately 10 day intervals without an antigenic stimulus. The patient was then maintained on a small daily dose of cyclophosphamide (50 mg/day). The inhibitor level responded to this therapy resulting in disappearance of the inhibitor and a progressive rise in the Factor VIII to levels greater than normal (170%). Our experience with these two cases suggests that a more rational approach to immunotherapy in the second case resulted in a sustained satisfactory immunosuppressive response.
Immunologic Studies in Patients with Von Willebrand’s Disease
Authors: Böttcher D. , Hasler K. , Sutor A.H.
Published: May 2019

An abnormal electrophoretic mobility of factor VIII related antigen(VIIIRAg) is a well known finding in patients with variants of von Willebrand’s disease (vWd), but it has also been described in patients with typical vWd. We have studied 12 patients with vWd and 5 members of a family with a variant of the disease, characterized by normal factor VIII activity and normal VIIIRAg but low or absent ristocetin cofactor activity. The electrophoretic mobility of VIIIRAg as measured by two dimensional immunelectrophoresis at pH 8.6 was grossly abnormal in all patients with a variant of vWd corresponding to the bleeding tendency. This correlation between clinical symptoms and abnormal electrophoretic mobility of VIIIRAg was not found in those patients with vWd, in whom the mobility of VIIIRAg was also grossly abnormal. Chromatography of cryoprecipitate from patients with the described variant of vWd revealed a delayed elution of VIIIRAg with a characteristic pattern, whereas the patients with typical vWd but abnormal electrophoretic mobility of VIIIRAg had normal elution patterns. It is suggested that an abnormal electrophoretic mobility of VIIIRAg is a common finding also in patients with typical vWd.
Carrier Detection in Hemophilia B.
Authors: Briët E. , Bertina R.M. , Tilburg N.H. van , Veltkamp J.J.
Published: May 2019

We examined 37 obligatory carriers of hemophilia B and 40 normal women. The levels of both factor IX activity and factor IX antigen were determined. The factor IX antigen levels were assayed in an inhibitor neutralization test in which a rabbit antiserum was used. 12 out of the 37 carriers had oral contraceptives and so did 20 out of the 40 normals.

Higher levels of both factor IX activity and factor IX antigen were found in the women, carriers as well as normals, using oral contraceptives. In carrier detection programs, therefore, a distinction should be made between women using the pill and those wo do not. The attempt to discriminate between carriers and normals on basis of factor IX activity and antigen levels proved to be as unsatisfactory as it was on the basis of factor IX activity levels only. The overlapping area of normals and carriers was smaller in the group of women on oral contraceptive medication. On the basis of our findings we expect that we can detect with a 90% confidence 17 carriers and 17 normals in a group of 100 potential carriers with an a priori chance on carriership of 50%. The detection rate is somewhat higher for women using oral contraception. The assay of factor IX antigen by means of the inhibitor neutralization assay does not appear to improve carrier detection.

Results with an immuno-electrophoretic assay of factor IX antigen will be discussed.
A Computer Analysis of Patient Activity and Blood Product Usage in Community Hospital Hemophilia Program
Authors: Lipton R.A. , Chin J.
Published: May 2019

This program evaluation assessed utilization of blood products and hospital services in 1975. One hundred eight hemophiliacs, 10 (0-4 years), 37 (5-12 years), 21 (13-18 years), 24 (19-30 years), 16 (30 years and over); 73 (Factor VIII), 20 (Factor IX), 12 (Von Willebrand’s Disease), and 3 (Factor XI) were categorized as to their severity and their primary treatment mode: Home Care Prophylactic, Home Care Episodic, Hospital-based Prophylactic, and Hospital-based Episodic Care. The results showed that the major user of hospital services was the child, 5-12 years. Hospital-based patients used more hospital based services, i.e., emergency room, comprehensive clinic, and dental non-surgery than did home based patients. In terms of factor unit consumption per kilogram body weight, prophylactic patients used the greatest amount of blood product. Children on prophylaxis missed less school but adults on prophylaxis did not miss less work. Children on hospital modes of care utilized this medical service less in the summer than did their peers on home based care. These results provided direction for planning future programs and staffing. They suggest a need for increasing surveillance of Home Care patients to maximize their participation in certain hospital based services. The unexpected finding of decreased hospital based care during the summer warrants further study. The results suggest considering prophylactic modes of care in school aged children.
A Family with an Unusual form of Factor VIII Deficiency
Authors: Dreher G.K. , Hall C.A. , Dodds W.J.
Published: May 2019

The propositus presented with post-traumatic and post-surgical bleeding suggestive of mild hemophilia. The factor VIII level was 21%; the bleeding time and platelet function assays were normal. Although 6 other male family members had similar bleeding histories, coagulation workups had not been performed on these or other relatives. Forty-three members were therefore studied in detail with the following findings: (1) factor VIII levels varied from 7.5-85% (mean - 36%) among affected males. (2) normal factor VIII-related antigens, factor IX and XI levels, and prothrombin complex activities. (3) much better correlation between bleeding histories and degree of prolongation of activated partial thromboplastin times than factor VIII activities. (4) inheritance that appears to be X-linked except that 6/6 grandsons of a carrier woman were affected, whereas 0/4 daughters of affected men had decreased factor VIII activity. These results are only partially consistent with a diagnosis of classical hemophilia A and suggest a variant form of hereditary factor VIII deficiency.
Replacement Therapy with a Factor VII Concentrate in Severe Factor VII Deficiency
Authors: Schimpf Kl. , Zimmermann K.
Published: May 2019

A 20 year old man, factor VII activity < 1%, was confined to bed since 1 1/2 years because of recurrent joint bleedings. Mobilisation became possible by means of a substitution therapy with a factor (f) VII concentrate (Immuno). The f VII content of the preparation was 25 units (u) per ml. After injection of 40 u of f VII per kg bodyweight (bw), the halflife time was 100 minutes. With injections of 33 u of f VII per kg bw every 6 hours, minimum levels of 50% prior to the next injection could be maintained. A steady perfusion with 1,6 u of f VII per kg bw and hour resulted in a level of about 35% f VII. Therefore, under these modes of administration an operation should be possible. Thus, we could perform a gastroscopia with several biopsies without any complication. An intensive physiotherapy was possible by giving 40. u of f VII per kg bw twice a day during 5 weeks. After changing to injections on need, we observed 5 elbow-bleedings within 4 months, which could be controlled with 2 times 40 u per kg bw at the day of bleeding. 5 months later, the patient could be discharged in home-treatment. He was now able to climb steps, to walk for about 500 m without a cane and to continue his professional education.
Hemophilia in Norway
Authors: Egeberg O.
Published: May 2019

Studies of all hemophilic families in Norway have resulted in the following distributions as to type and degree of factor defects.

Of the hemophilia B families, 3 were of the type BM. In connection with multiple transfusions to patients with severe hemophilia A, 13 patients developed severe abnormal inhibitor to f.VIII, 3 of them died. In several other such transfused hemophilia A patients, weaker coagulation inhibitory activities have been demonstrated.