Impact of new AABB guidelines on hepatitis B and C testing among Saudi blood donors.

This study aims to compare the advantages and disadvantages of implementing the new American Association of Blood Banks (AABB) guidelines for hepatitis B and C against its old criteria for screening blood donors. Between July 1995 and December 2002, 63,368 consecutive blood donors were screening for hepatitis B and C according to the new guidelines. Cost and prevalence were analysed and compared with those found using the old AABB guidelines prior to July 1995. The overall percentage rate of deferred donors showed a significantly decrease to 19.3% in 2002, compared to 58.4% before July 1995 (P < 0.001). The new prevalence of hepatitis B and C among Saudi blood donors was found to be 1.7% and 0.6%, respectively, compared to 4% and 1.4%, respectively, under the old AABB guidelines. This resulted in a significant increase in the number and yield of blood units, and a decrease in the prevalence of hepatitis B and C was observed among screened donors. Using the new AABB guidelines, the estimated direct cost of donor screening for hepatitis B and C decreased significantly from 42.8 dollars per donor to 29.2 dollars per donor (P<0.001).

HIV-1 p24 antigen testing in blood banks: results from Saudi Arabia.

HIV-1 p24 antigen testing was introduced to increase sensitivity in the early detection of HIV infection in blood donors. Since the introduction of HIV-1 p24 antigen testing in Saudi Arabia, we have failed to detect a single positive case. Over a three-year period, only four indeterminates were detected out of 24,654 blood donors. All four proved negative by confirmatory testing. Based on this experience, we believe that resources would be better directed to pooled nucleic acid testing and that p24 serological testing should be abandoned.

International forum: Saudi Arabia. Donor screening for HTLV-I in Saudi Arabia: is it cost effective?

After screening over 100,000 blood donations for the presence of anti-HTLV-I antibodies, a final prevalence of 0.0038% was established in a multinational donor population. Among 38,201 donations by Saudi Arabian donors, the prevalence was found to be 0.0052%. Fifty-eight donors were found to be repeat reactive in the EIA screen test, but only 6.9% of these (n = 4) were truly infected with HTLV-I as judged by the Western blot result. These results indicate that Saudi Arabia is non-endemic for HTLV-I as well as HTLV-II. The cost effectiveness of screening for HTLV-I in healthy blood donors from this area is highly questionable. Calculations point to a final risk of a case of post-transfusion HTLV-I associated disease of approximately one per 100 years at the current level of activity.

Hepatitis B core antigen antibody as an indicator of a low grade carrier state for hepatitis B virus in a Saudi Arabian blood donor population.

Blood donor screening for anti-hepatitis B core antigen (anti-HBc) was introduced as a surrogate marker of non-A, non-B hepatitis prior to the availability of a specific test for hepatitis C. In areas endemic for hepatitis B virus (HBV), such as Saudi Arabia, earlier studies indicated that up to 30% of blood donors might disqualify if screened for anti-HBc. The issue was readdressed in a study of 6035 consecutive first-time Saudi national blood donors in an attempt to identify a subgroup of anti-HBc positive donors who might be at high risk of being low grade carriers of HBV. An isolated anti-HBc of high titer in a donor with a low or absent anti-hepatitis B surface antigen (anti-HBsAg) was taken as an indicator of increased risk of a low grade carrier state. Using this algorithm, an additional 125 (2%) donors would disqualify. HBsAg immune complex assays and polymerase chain reaction of donor samples with an isolated anti-HBc identified two donors with immune complexes and two donors with HBV DNA. All four donor samples expressed over 90% neutralization in the anti-HBc supplementary testing, indicating high titer anti-HBc. These findings seem to support the suggested policy of donor exclusion based on the anti-HBc and anti-HBsAg serology as a means to eliminate low grade carriers of HBV in endemic areas without jeopardizing the blood supply.

Mild haemophilia A in Iceland: clinical genetic studies of three families with the same mutation.

OBJECTIVES: The aim of the study was to define the phenotype in three families with mild haemophilia A and to determine restriction fragment length polymorphisms (RFLP), which could support a hypothesis of a common progenitor of the families. DESIGN: Family survey. SETTING: Index cases were identified in and outside hospital and a family survey for symptoms and signs of bleeding in family members and sampling for coagulation and RFLP studies were mostly carried out in the field. SUBJECT: Family members with and without symptoms of bleeding were selected for investigation and normal spouses and unrelated individuals were investigated for control. INTERVENTIONS: Medical advice regarding affected family members were given to the families and their physicians. MAIN OUTCOME MEASURES: Bleeding time, factor VIII activity, quantification of factor VIII:Ag, von Willebrand factor (vWF) Ag and vWF ristocetin assay. Typing of RFLP polymorphisms for genetic homogeneity. RESULTS: Bleeding manifestations are present in both sexes in the three families although more frequent and more severe in the males. The level of factor VIII activity is between 10 and 20% in most affected males whereas 35-60% is found approximately in 2/3 of female carriers and in 1/3 of them factor VIII activity is within the normal range. It is suggested that screening for this mild haemophilia A gene by a molecular genetic method would be of clinical value now, its mutation having been detected. CONCLUSIONS: Transmission of mild haemophilia A through six to seven generations is demonstrated by the study. The mild haemophilia A type described is the most prevalent of haemophilia A types in Iceland (population 260,000, 1992). The founder effect was confirmed by studies of RFLP polymorphisms.

Second-generation anti-HCV screening in a Saudi Arabian donor population.

The 2nd-generation anti-HCV test system was applied to a Saudi Arabian multi-ethnic donor population. When donors were stratified according to first-time donations versus repeat donations, the latter having been screened previously by a 1st-generation set of tests, it was found that in Saudi Arabian and Middle East nationals, the 2nd-generation tests (EIA and RIBA), identified close to double the number of anti-HCV-positive donors, compared to an earlier study using the 1st-generation tests. Part of this finding was due to a 38% higher rate of RIBA-confirmable repeat-positive EIA results. In groups of donors, previously screened by the 1st-generation system, some additional cases of anti-HCV reactivity were identified, most prominently in Middle East nationals. It is assumed that some of these represented recent seroconversions, while others were cases of serologic subtypes of HCV, not reacting in the 1st-generation tests. The current test system identifies 0.66% of Saudi-Arabian, and 2.87% of other Middle East donors as putative carriers of hepatitis C virus. The study lends support to the opinion that donors who return regularly over the years have a lower prevalence of disease markers, thereby being a safer source of blood than first-time donors.

Histologically advanced chronic hepatitis C treated with recombinant alpha-interferon: a randomized placebo-controlled double-blind cross-over study.

Chronic hepatitis C is common in Saudi Arabia and most often presents in an advanced stage. To assess the response of patients to interferon, a randomized placebo-controlled double-blind study was undertaken. All but 1 patient had cirrhosis or fibrosis before interferon. After a 24-week observation period patients received alpha 2a interferon, 3 mega units sc tiw or placebo for 24 weeks, then the opposite treatment for another 24 weeks followed by 24 weeks of observation. Liver biopsies were performed before and after each of the treatment phases. Twenty-two out of 24 patients completed the study. The mean alanine aminotransferase (ALT) levels fell from 150.7 +/- 118.7 units/l to 91.0 +/- 42.6 units/l after 6 months interferon treatment (P = 0.03) but only 3 patients (14%) had complete normalization of mean ALT levels and 4 (18%) had > 50% reduction. The mean hepatitis activity index fell from 12.2 +/- 2.6 immediately before to 11.6 +/- 2.5 just after interferon (P = 0.4). After interferon there was an insignificant raise in 6-month mean ALT. Hepatitis C virus-RNA was positive in all 17 patients tested and remained so after treatment. Side-effects were mild and well tolerated. Alpha interferon 3 mega units tiw for 24 weeks is not an effective treatment of histologically advanced chronic hepatitis C.

Chronic non-A, non-B hepatitis complicated by end-stage renal failure treated with recombinant interferon alpha.

Chronic non-A, non-B hepatitis occurs in 50% of Saudi patients with end-stage renal failure and requires long-term hemodialysis since it is a contraindication to renal transplantation. Thirteen patients with biochemical and histological documented chronic non-A, non-B hepatitis (11 with HCV antibodies) entered a double-blind placebo controlled cross-over study, in which Roferon A 3 MU or placebo were administered subcutaneously 3 times weekly after hemodialysis for 6 months. The mean ALT fell significantly from pretreatment levels of 74.7 (95% confidence interval (CI) 54.7, 92.5) (13 patients in the 6-month run-in period) and 66.8 (CI 47.7, 85.8) (7 patients in the run-in period + 6 patients in the placebo period) (difference NS) to 37.6 (CI 21.0, 54.2) during interferon treatment (P < 0.005). In 10/13 patients (77%) ALT levels became normal. In the 6-month follow-up period immediately after therapy, the mean ALT was 45.2 (CI 28.0, 62.0). Although this change was not significant (P = 0.49), only 7 of these 10 patients sustained biochemical remission in the 6-month follow-up period. The corresponding total Histological Activity Index improved from 8.9 (CI 7.5, 10.3), 8.9 (CI 7.2, 10.7) (difference NS) to 6.2 (CI 3.9, 8.5) (P < 0.05; P = 0.052, respectively). Intralobular inflammation and periportal inflammation showed the most significant changes. Five of 13 (39%) and 2/13 patients (15%) had complete resolution of piecemeal necrosis and intralobular inflammation, respectively. Toxic effects of interferon were mild, early and self-limiting.(ABSTRACT TRUNCATED AT 250 WORDS)

HTLV-1 antibody testing in a Saudi Arabian blood donor population.

Human-T lymphotrophic virus Type 1 may be transmitted by cellular blood products. A low but definite risk exists that recipients of HTLV-1 infected products may develop severe even fatal disease. After one year of screening for HTLV-1 antibodies in 12,851 units of blood collected from a multinational volunteer donor population of which 42.6% were Saudi nationals, we found two units of blood which reacted repeatedly positive in the screen test. In both cases, the Western Blot confirmatory test was indeterminate in that not all bands required for a positive reaction were present. Both donors were expatriates from North America either living in an endemic area or with Caribbean ancestors. Although more than 5,000 Saudi national donors were tested and found negative for HTLV-1 antibodies, a statistical estimate of the maximal risk of finding a positive donor in this donor population subgroup is in the order of 0.055%. Based on these results it is recommended that blood banks in this region screen for HTLV-1.

Hepatitis C antibody prevalence in Saudi Arabian blood donor population.

Based on the screening of 10,646 units of blood by a recombinant hepatitis C antibody enzyme-linked immunosorbent assay (ELISA), the prevalence of hepatitis C (HCV) antibody-reactive donors was established in a Saudi Arabian donor population. The overall prevalence of HCV antibody was found to be 1.01%. By nationality, the antibody frequency was 1.00% (Saudi males), 2.30% (other Middle Easterners), 0.71% (Far East nationals), and 0.39% (Europeans/North Americans). The ELISA HCV antibody reactive units were further tested by a recombinant immunoblot assay (RIBA) in which 47.2% of the initially reactive samples were found to contain specific antibodies to two recombinant antigens. HCV antibody seroprevalence defined by reactiveness in both tests was 0.48% for the entire population, 0.33% (Saudis), 1.42% (Middle Easterners), 0.27% (Far East nationals and Europeans/North Americans). The surrogate markers alanine aminotransferase (ALT) and hepatitis B core (HBc) antibody identified 7.7 to 40% and 20 to 56.4%, respectively, of donors of different nationalities testing repeatedly reactive in the HCV ELISA. Likewise, ALT and HBc antibody identified 20 to 57.1% and 0 to 66.75%, respectively, of HCV ELISA and RIBA reactive donor samples, depending on nationality. It was concluded that the present anti-HCV testing, althought useful in screening blood for HCV carriers, must be supplemented by surrogate tests until additional specific tests are available.

Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery.

We carried out a placebo-controlled, double-blind, randomized study of the hemostatic effect of tranexamic acid mouthwash after oral surgery in 39 patients receiving anticoagulant agents because of the presence of cardiac valvular stenosis, a prosthetic cardiac valve, or a vascular prosthesis. Surgery was performed with no change in the level of anticoagulant therapy, and treatment with the anticoagulant agent was continued after surgery. Before it was sutured, the operative field was irrigated in 19 patients with 10 ml of a 4.8 percent aqueous solution of tranexamic acid (an inhibitor of fibrinolysis) and in 20 patients with a placebo solution. For seven days thereafter, patients were instructed to rinse their mouths with 10 ml of the assigned solution for two minutes four times a day. There were no significant differences between the two treatment groups in base-line variables, including the level of anticoagulation at the time of surgery. Eight patients in the placebo group had a total of 10 postoperative bleeding episodes, whereas only 1 patient in the tranexamic acid group had a bleeding episode (P = 0.01). There were no systemic side effects. We conclude that local antifibrinolytic therapy is effective in preventing bleeding after oral surgery in patients who are being treated with anticoagulants.

Preparation of packed red cells suitable for intravascular transfusion in utero.

Intra-cardiac transfusion in utero is a recent development in the treatment of erythroblastosis foetalis. As with intra-umbilical cord transfusion, the procedure has been described as having a high risk of complication characterized by bradycardia and cardiac-arrest. Intra-coronary hyperkalemia was suspected as being a major contributing factor towards the complications experienced, particularly by the intra-cardiac delivery. The procedure is warranted, however, in cases where intra-umbilical cord transfusion is not possible. Therefore, studies comparing various methods of preparing packed cells for intravascular transfusion were initiated. The plasma potassium levels of gravity sedimented packed cells and saline washed red cells resuspended in either Ringer's lactate, pooled donor plasma or saline were measured. Products of saline washed/resuspended packed red cells transfused within 2 hours of preparation were found to have low potassium levels while exposing the fetus to minimal risk of transfusion transmitted infection and were therefore selected to be the most suitable product. Using this product, a significant decrease in the incidence of severe bradycardia resulting in cardiac-arrest, following intravascular transfusion (32 procedures) was observed.

Clinical experience with human plasma-derived factor VIIa in patients with hemophilia A and high titer inhibitors.

FVIIa purified from human plasma and spontaneously activated during the purification procedure was given to 4 patients with hemophilia A and inhibitors against FVIII:C in association with joint bleeds. A dose of 9-20 micrograms/kg b.w. (700-1,000 U/kg b.w.) seemed to be hemostatically active in moderate to severe joint bleeds. Plasma levels of FVII of 5-7 U/ml were achieved and recoveries varied between 17 and 66%. The lower recovery rates of 17-39% were all found in 1 of the patients. No immediate side effects were seen. Neither were any signs of a systemic activation of the coagulation system observed. It is concluded that highly purified FVIIa may be useful in the treatment of hemophilia A patients with inhibitors against FVIII:C.

Near normoglycemia for 1 year has no effect on platelet reactivity, factor VIII, and von Willebrand factor in insulin-dependent diabetes mellitus: a controlled trial.

The impact of prolonged near-normoglycemia on platelet reactivity (spontaneous and induced platelet aggregation), factor VIII, and von Willebrand factor in patients with insulin-dependent diabetes mellitus (IDDM) was evaluated in a prospective, randomized, controlled clinical trial. Twenty IDDM patients with no or only minor clinical signs of microvascular disease were randomly assigned to 1 year of continuous subcutaneous insulin infusion (CSII) or unchanged conventional insulin treatment (CIT). Hemoglobin A1c declined during the 12 month observation period from 7.3 +/- 1.2% to 6.4 +/- 0.9% (2p less than 0.01) in the CSII group, while this measure of glycemic control was unchanged in the CIT group: 7.2 +/- 1.1% vs 8.0 +/- 1.6% (NS). Platelet reactivity, factor VIII, and von Willebrand factor concentrations were identical in the two groups at entry into the study, and no significant changes in these variables were seen in either group. Thus, the present results do not support the concept of increased platelet reactivity following CSII treatment.