Subcutaneous infusion ports in the pediatric patient with hemophilia.

Central venous access devices have become important tools in the management of pediatric patients with malnutrition, malignancy, and infections requiring long-term antibiotic treatment. Hemophilia presents a lifetime challenge for venous access and at times can be an urgent or life-threatening situation. Since 1986, the authors have implanted 11 subcutaneous infusion ports in nine patients with hemophilia. The systems have remained in place for up to 7 years, without major complications or problems. Two catheters were replaced, after 4 and 6 years, because of skin erosion and blockage, respectively. One catheter was removed after 7 years because of blockage following local trauma and was not replaced. A recent survey through the Canadian Hemophilia Centre Directors Group obtained a further 45 subcutaneous infusion ports in other centers across Canada. The benefits of this system are overwhelming enthusiasm by the parents and children and no major complications. Some of the patients are now HIV-positive and are able to use their system for ongoing drug therapy.

Computer assisted serum/biological fluid storage: hemophilia serum/plasma bank.

Samples are drawn from hemophiliacs to retrieve plasma and serum for testing and storage. The samples for testing are tested and the results compiled using a database computer program. The samples for storage are coded and stored at -70 degrees C under controlled conditions. The location of the samples is then entered into the database computer program. The results of the tests, or the stored sample location, can be easily retrieved using the computer.

Multiple pyarthrosis in human immunodeficiency virus-infected hemophiliacs.

Classically, a swollen, painful joint in a patient with hemophilia has been considered to be due to a hemarthrosis until otherwise proven, and treated immediately with appropriate coagulation factor replacement. Two cases of human immunodeficiency virus (hiv)-infected hemophiliacs presenting with an initial apparent hemarthrosis, complicated subsequently by numerous pyarthroses and sepsis are described. In light of the prevalence of hiv infection in the adult hemophiliac population with arthropathy, a reappraisal of the clinical caveat of immediate infusion without joint aspiration is required.

Lupus anticoagulant testing: effect of the platelet count on the activated partial thromboplastin time.

The activated partial thromboplastin time (APTT) is often used as a test to diagnose patients with lupus anticoagulants. It is recommended that platelet-poor plasma be used in the APTT test. In this study the effects of residual platelet contamination on lupus anticoagulant and antiphospholipid antibody testing are described. In fresh samples the residual platelet contamination has no significant effect whereas in frozen samples the effect of residual platelet contamination can have a significant effect on the APTT testing.

Bacterial-induced activation of erythrocyte T-antigen complicating necrotising enterocolitis: a case report.

Erythrocyte Thomsen-Friedenreich crypt antigen (T-antigen) activation is not an uncommon event in infants with severe necrotising enterocolitis (NEC). Transfusion of these infants with blood products containing plasma carries the risk of causing intravascular haemolysis. T-antigen activation is easily detected using a rapid simple lectin agglutination test. Early recognition of T-antigen activation ensures the correct choice of plasma free transfusion therapy. We describe an infant with severe NEC complicated by T-antigen activation and haemolysis.

Absence of human T-lymphotropic virus types I and II infection in an Ontario hemophilia population.

Two hundred ninety-three serum samples from Ontario hemophiliacs and 200 samples from human immunodeficiency virus-positive blood donors were screened for the presence of antibodies to human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunosorbent assay, radioimmunoassay, and Western blot techniques. None of the serum samples provided unequivocal positive results, but several samples gave inconclusive results. Of the hemophiliacs with inconclusive serologic results from whom peripheral blood lymphocyte DNA could be obtained, all were negative for HTLV-I and HTLV type II (HTLV-II) sequences as determined by polymerase chain reaction (PCR). PCR was also performed on a lymph node biopsy sample taken from a hemophiliac who developed a rare T-cell lymphoma; the sample was negative for HTLV-I and -II sequences. These results indicate that Ontario hemophiliacs have not been exposed to HTLV-I or HTLV-II.

Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant Factor VIII Study Group.

BACKGROUND: Current treatment of hemophilia A, a hereditary disorder affecting approximately 1 in 10,000 males, relies on plasma-derived factor VIII concentrates. We tested the safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder. METHODS: We conducted the investigation in three stages: comparing the pharmacokinetics of plasma-derived and recombinant factor VIII, assessing the efficacy of recombinant factor VIII for home therapy, and assessing its efficacy for major surgical procedures and hemorrhage. A total of 107 subjects with hemophilia, 20 of whom had not been treated previously, enrolled in the investigation. RESULTS: The in vivo recovery and elimination half-lives of recombinant factor VIII equaled or exceeded those of plasma-derived factor VIII. Seventy-six subjects participated in a home-treatment program, using recombinant factor VIII for 69 to 807 days (median, 618); home diaries of 56 subjects treated for 5 months were analyzed. Of 540 bleeding episodes, 399 (73.9 percent) required only one treatment with recombinant factor VIII. The projected annual consumption of recombinant factor VIII was similar to that of plasma-derived factor VIII concentrate. Twenty-six subjects received recombinant factor VIII for 22 surgical procedures and 10 serious hemorrhages; hemostasis was excellent in all cases. De novo formation of inhibitors occurred in only 1 of 85 previously treated subjects. Inhibitor antibodies also developed in 6 of 21 children, 20 of whom had not previously been treated; 5 had low levels (less than or equal to 7.5 Bethesda units) despite continued treatment with recombinant factor VIII. There was no evidence of new formation of antibody to foreign proteins, and recombinant factor VIII was well tolerated. CONCLUSIONS: Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.

Prescribing and dispensing practices for oral iron tablets: a Canadian experience.

The formulation of an oral iron tablet may influence its therapeutic efficacy in correcting iron deficiency. In order to determine the oral iron preparations patients in a Canadian urban center were receiving, a questionnaire was circulated to family physicians, internists, surgeons, and obstetrician-gynecologists to determine their prescribing practices. A survey of pharmacies in the city was also conducted to determine which brand of each iron salt (sulfate, gluconate, fumarate) they dispensed for a generic oral iron prescription. Most physicians (74 percent) chose ferrous sulfate as their drug of first choice. The majority of prescribers would not specifically request either enteric-coated/slow-release or nonenteric-coated preparations as first or second choices (71 and 64 percent, respectively). Enteric-coated or slow-release preparations were specified by 10 and 19 percent of physicians as first and second choices, respectively. Most pharmacies (96 percent) dispensed an enteric-coated preparation of ferrous sulfate for a generic prescription. We believe that many patients are receiving iron tablets with altered release properties (enteric-coated/slow-release). These tablets may fail to provide the desired therapeutic benefit based on the known physiology of iron absorption.

Sensitivity of the thrombin clotting time and activated partial thromboplastin time to low level of antithrombin III during heparin therapy.

The thrombin clotting time (TCT) has been used at our institution, along with the activated partial thromboplastin time (aPTT), for monitoring heparin therapy. We have observed that, in some patients, a discrepancy develops between the heparin levels predicted by the TCT and the aPTT with the TCT consistently predicting a lower heparin level than the aPTT. An inverse relationship was noted between the functional antithrombin III (AT-III) level and the magnitude of this discrepancy.

Intramuscular administration of iron during long-term chelation therapy with 2,3-dimercaptosuccinic acid in a man with severe lead poisoning.

2,3-Dimercaptosuccinic acid (DMSA) an investigational chelant structurally similar to dimercaptopropanol (BAL), offers the advantage of not depleting iron stores on which basis it would not seem to form a toxic chelate with iron. We report the case of a man with a formidable body burden of lead (Pb) and depleted iron stores who was given iron intramuscularly during a defined period of long-term retreatment with DMSA. Initiation of retreatment with DMSA, 30 mg/kg/day given orally in three divided doses for the first 7 days markedly enhanced Pb diuresis, entailed a pronounced fall in blood Pb and abolished symptoms of Pb poisoning. Continuation of retreatment with two-thirds the initial DMSA dose for an added 15 days maintained blood Pb at sustained low levels. Iron sorbitol administered intramuscularly during this period in individual doses of 100 mg of elemental iron given 3 days apart to a conservative total of 400 mg produced no untoward effects, suggesting that a toxic chelate between iron and DMSA was not formed. Serum ferritin entered the normal range and there was virtually an immediate significant decrease in erythrocyte protoporphyrin. Together with discernible increases in haemoglobin, haematocrit and MCV, this pointed to enhanced iron utilization. Since iron utilization is curtailed by high concentrations of Pb, the immediacy and magnitude of the post-chelation rebound in blood Pb precluded iron administration at any other stage. From these data, DMSA emerges as a uniquely versatile new chelant. Suitable for long-term administration, it permits the simultaneous parenteral administration of iron during dose-related sustained decreases in blood Pb.

An audit of blood component therapy in a Canadian general teaching hospital.

As part of a quality assurance program a retrospective audit of transfusion practices for packed red blood cells, fresh frozen plasma and albumin was undertaken with predetermined criteria in a general teaching hospital. Of 520 transfusion episodes with 1218 units of packed red blood cells given to 297 patients 88% were considered appropriate; of 106 episodes with 405 units of fresh frozen plasma given to 83 patients 90% were deemed appropriate; and of 187 episodes with 320 units of albumin given to 99 patients 64% were considered appropriate. The results of this audit, when compared with those of other surveys of blood use in a similar population, suggest that pretransfusion approval of requested components would reduce the number of inappropriate transfusions.

Carrier detection in hemophilia A: ABO blood group, multiple measurements, and application of logistic discrimination.

In healthy 20- to 50-year-old women, the ABO blood group has a significant effect on levels of von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) and on factor VIII activity (F.VIII:C). However, there is no significant effect of ABO group or subject age on the ratio log e(F.VIII:C/VWF:Ag). Multiple measurements of the "ratio" on possible carriers of hemophilia A may be combined with pedigree information using logistic discrimination to yield final risk assessment. To reduce misclassification of carriers as normal women, a lower limit, specified by the logistic model, is set on the logistic carrier probabilities. In this study, the proportion of blood group A for a population of obligate carriers was significantly higher than that expected for the general population (60% vs. 42%); for a population of control women it was lower than expected (22.5 vs. 42%). The effect for the carriers came primarily from daughters of affected fathers, as 81.3% were of blood group A. These observations indicate that a "universal" discriminant should be applied with caution.

A comparison of the availability and content of genetic counseling as perceived by hemophilic men and carriers in the U.S.A., Canada, Scotland, and Greece.

A survey study was carried out with 211 hemophilic men and 205 carriers of hemophilia at four hemophilia centers in New York; London, Ontario; the West of Scotland; and Athens, Greece. The participants responded to a questionnaire exploring socio-demographic and medical information, attitudes toward hemophilia, and experience of and attitudes toward genetic counseling. The study shows differences between attitudes of hemophilic men and carriers, differences in perceived problems among patients and carriers in the four centers, and differences in opinions between consumers and professionals. Comprehensive services for hemophilic families available in the New York center facilitate both patient education and satisfaction.