HLA alloimmunization in patients receiving multitransfusions of red blood cells.

HLA antibodies were studied in 88 patients with chronic hemolytic anemia who received multitransfusions of red blood cells prepared by conventional (PRC-C), inverted centrifugation (LR-I) and leukocyte filter (LR-F) techniques. Their mean age was 8 years and 4 months with a duration of transfusion of 8 years. The patients were divided into five groups: group 1, receiving PRC-C (n=20); group 2, receiving LR-I (n=33); group 3, receiving LR-F (n=11); group 4, subsequently receiving LR-I and LR-F (n=10); and group 5, receiving PRC-C followed by LR-I and LR-F (n=14). The HLA class I antibodies were found in 30 out of 88 patients (34%). All were against HLA antigens commonly found in the Thai population. The patients receiving PRC-C exhibited HLA antibodies of 65%, which was significantly higher than those of patients receiving LR-I (24%) and LR-F (0%). Consequently, the transfusion reactions of fever, chill, rash and urticaria were also commonly found in patients receiving PRC-C (13.4%), which was significantly higher than patients receiving LR-I (0.4%) and LR-F (0%). The leukocyte filter technique has been shown to be effective in preventing HLA alloimmunization and transfusion reactions but the price is rather high. For the inverted centrifugation technique, only transfusion reactions were effectively prevented and the HLA alloimmunization continued to develop. A more effective and low-cost method for the removal of leukocytes should be investigated for these multitransfusion patients.

The efficacy and safety of lyophilized cryoprecipitate in hemophilia A.

This prospective study of assessing the efficacy and safety of lyophilized cryoprecipitate (LC), which was heat-treated at 60 degrees C for 25 hours, was conducted in 23 patients with hemophilia A (severe 13, moderate 9, mild 1) at the International Hemophilia Training Center, Bangkok from 1997 to 1998. A total of 223 infusions of LC were given. The status of the patients could be classified into 4 groups: group I, non-bleeding (n = 13); group II, severe bleeding requiring hospitalization (n = 9); group III, appendectomy (n = 1) and group IV, early bleeding controlled by modified home treatment (n = 200). Pharmacokinetic studies were conducted in groups I and II. The mean in vivo half-life of factor VIII clotting activity (F VIII:C) was 12.6 hours and the mean in vivo incremental recovery at baseline was 2.1 per cent/unit/kg. The mean clearance was 3.22 ml/kg/h. There was no statistically significant difference in these parameters between groups I and II (p > 0.05). The hemostasis was successfully achieved and 1 to 2 small urticarial wheals were observed in only 2 infusions. In addition, 9 out of 23 patients received LC exclusively for 1 year. None of them developed inhibitor to F VIII:C nor did any contract additional transfusion-transmitted infection except one who developed anti-hepatitis C virus seroconversion after receiving 16 bottles of LC in 4 months. Therefore, the more efficient virus-inactivation in the preparation of LC should be established.

Home treatment for patients with congenital bleeding disorders in a developing country.

Ninety-six patients with congenital bleeding disorders were enrolled in a home treatment program from 1979 to 1997. The diagnosis included severe and moderate hemophilia A and B (n = 63), mild hemophilia A (n = 18), von Willebrand disease (vWD) (n = 12) and congenital factor VII deficiency (n = 3). The median age was 9 years and the median duration of follow-up was 4 3/12 years. The home treatment was modified 4 ways: (1) Using locally-prepared single units of fresh dry plasma in the majority of the patients while mild hemophilia A and vWD patients received 1-deamino 8D-arginine vasopressin. (2) Recruiting local health personnel as the primary care providers. (3) Teaching and training patients and parents intensively. (4) Maintaining an effective control system. The heartful effort of the health personnel was not in vain; the patients learned to take good care of themselves. Twenty patients and 20 parents or relatives were able to perform venipuncture properly and no adverse effect was observed. Since the hemorrhage was treated very early, the severity and sequelae of bleeding were decreased. The utilized blood components and days of hospitalization were reduced. Impressively, the absenteeism from work or school was minimized so that the patients could enjoy a near normal life in their family, school and society.

Low cost locally prepared fibrin glue for clinical applications: reported of 145 cases. Committee of Bangkok International Hemophilia Training Center.

Fibrin glue (FG) is one of the blood products known to be very useful for local hemostatic measure and as a medically valuable tool for adhesion, sealing, anastomosis, repair microvascular and nerve grafts in medical and surgical procedures. Before 1996, FG was used to a limited extent in Thailand due to the high cost. Technology for locally prepared FG was transferred to Bangkok International Hemophilia Training Center of the World Federation of Hemophilia (IHTC-WFH) in July 1996 by Prof. Uri Martinowitz and the late Prof. Henri Horoszowski. Since then FG has been widely used and proved to be very useful in Thailand. This paper reports 145 cases using low cost locally prepared FG at Ramathibodi Hospital during November 1996 to December 1997. A total of 145 cases with age range from 5 months to 73 years, which included 55 pediatrics and 90 adults, 100 males and 45 females. The amount of FG used was 1-80 ml per case. Clinical procedures included dental surgery (46), open heart surgery (35), ENT (28), orthopedic (13) including 2-3 joint correction in one session in 2 hemophiliacs, neurology (11), plastic repair (7), liver (2) and severe bleeding in dengue hemorrhagic fever (3). Forty-seven cases had hemostatic disorders. The result of local hemostatic, adhesive and sealant effect of FG was satisfactory with no complications. In open heart surgery, the amount of content in chest drain decreased and none required reopen-surgery to stop bleeding. Dental surgery was performed in 43 patients with bleeding disorders i.e. hemophilia, idiopathic thrombocytopenic purpura, leukemia, severe thrombocytopenia, patients on anticoagulant, etc. Only 3 cases (7%) required blood component compared to all of the 50 no-FG controlled cases (100%) that required blood component therapy. FG has proved to be very useful in many aspects i.e. minimizing blood product usage, decreasing medical workload, reducing medical cost and increasing patients' convenience and satisfaction in particular.

Vitamin K deficiency bleeding in Thailand: a 32-year history.

Vitamin K deficiency bleeding cases in Thailand from 1963 to 1995 were extensively studied. From 1963 to 1987 there were 499 reported cases from 10 papers including 102 cases of the authors' series. From March 1994 to April 1996, two subsequent nationwide surveys were conducted where questionnaires were sent to 714 and 732 hospitals located throughout Thailand. The responding rate was 58.2% and 67% respectively. 331 cases were found during 1988 to 1995. The total number was 830 cases of which 799 were idiopathic vitamin K deficiency in infancy (IVKDI) and 31 were secondary types. IVKDI was found exclusively breast-fed infants (92%) who did not receive vitamin K prophylaxis at birth (90%). Bleeding and pallor were the common features. The occurrence of intracranial hemorrhage was strikingly high (82%); the fatality rates was 24%. However, the fatality rate among patients receiving either 1 mg of vitamin K, intramuscularly, (17%) or 2 mg, orally, (18%) were lower than those not receiving vitamin K prophylaxis (36%). The incidence of IVKDI significantly declined to 4.2-7.8 per 100,000 births between 1988 to 1995 which was in reverse proportion to the coverage of vitamin K prophylaxis (r = -0.94, p < 0.05).

Eluding transfusion-transmitted HIV infection: report of two cases.

Two hemophilia A boys (FVIII: C < 1% and 2.2%), whose ages were 12 and 14 years. old, received fresh frozen plasma of 140 ml and 210 ml, respectively, in 1989. It was the 27th and 13th donation for each regular donor who was negative for anti-HIV testing. However, both donors had HIV seroconversion within 95 to 110 days after the last donation. They might have contracted HIV infection shortly after the last donation. Luckily, the two hemophiliac recipients are still in good health and negative for anti-HIV and HIV-antigen testings for 7 years.

Prophylactic treatment for hemophilia A patients: a pilot study.

Prophylactic treatment with factor VIII concentrate was given to six hemophilia A boys whose factor VIII:C ranged from 1% to 3.5% at Ramathibodi Hospital. The age ranged from 11 to 16 years with the median age of 12 years old. Each patient received factor VIII concentrate twice a week in the dosage of 8-10 unit per kg for one year. During the prophylactic period, bleeding episodes seldom occurred. They did not need hospitalization. The absence from school was reduced. They became muscular from regular daily exercise. They could join the activity at school and lived a near normal life. The patients and family were very happy since they did not have to worry about bleeding. No adverse effect was found. The only constraint was the cost. It cost 180,000 baht (US$ 7,200) per year or 15,000 baht (US$ 600) per month for a 25 kg hemophiliac boy.

Thrombotic risk of children with thalassemia.

Pulmonary microthromboembolism is one of the serious complications found in patients with thalassemia. The pathogenesis is undetermined. The thrombotic risk in 44 patients (26 males, 18 females) with beta-thalassemia/hemoglobin E disease and without clinical symptoms of thrombosis were studied. The age ranged from 3-19 yr (X +/- SD = 10 +/- 4). Neither of them had chronic hepatitis B infection. They were divided into three groups according to clinical manifestations as follows: (1) Mild form (n = 12). They did not require blood transfusion. The mean +/- SD of hematocrit was 23.3 per cent +/- 2.3; (2) Severe form (n = 19). They required frequent blood transfusion. The mean +/- SD of hematocrit was 17.7 per cent +/- 1.5; (3) Severe form with splenectomy (n = 13). They seldom required blood transfusion. The mean +/- SD of hematocrit was 21.8 per cent +/- 3.5. Most of the patients had delayed growth. They had high serum ferritin reflecting iron overload status which was prominent in the severe groups (group 2 & 3). The prothrombin time and serum albumin were slightly decreased, and the serum alanine transaminase were slightly increased; all of which reflected mild alteration of liver function. The plasma AT III, PC and PS antigen in the three groups were similar. The mean +/- SD of AT III antigen was 106.7 per cent +/- 22.2 which is normal. The mean +/- SD of PC antigen was 44.2 per cent +/- 14.2 and PS antigen level was 77.2 per cent +/- 17.8.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatopathy-thrombocytopenia vs infection-induced hemophagocytic syndrome in Wilms' tumor: a case report.

A 3-year-old boy with Wilms' tumor, post operative left nephrectomy stage, had HTS on day 99 of the combined chemotherapy which lasted for more than 20 days. He had severe respiratory distress due to a moderate amount of ascites and marked pleural effusion. Because of high fever, thrombocytopenia and marked hemphagocytosis in the bone marrow, he received IVIG for 2 days. Normal platelet count and markedly decreased pleural fluid were attained within 3 days. He subsequently tolerated full doses of combined chemotherapeutic agents with an additional one (doxorubicin). In cases of HTS, IAHS should be suspected. The bone marrow should be done and treatment accordingly so that there is no need to decrease, the dosage of chemotherapeutic agents afterwards.

Disseminated Burkitt's lymphoma in a child with AIDS.

Rarity of HIV-associated disseminated lymphomas in children initiated this report. The patient was an 18-month-old girl who had a history of chronic cervical lymphadenopathy since 6 months of age. She was first seen because of rapid enlargement of an inguinal lymphnode. The bone marrow aspirate was compatible with Burkitt's lymphoma, L3 cell-type. She was treated with chemotherapy without satisfactory success. She developed neurological involvement of lymphoma. Accidental sharp injury which contaminated her blood, in a medical personnel leaded to having her blood tested for anti-HIV and it was found positive. Her mother had positive anti-HIV presumably acquired from blood transfusion after an abortion in early 1988. It occurred before the donated blood was compulsively tested for anti-HIV. She died at the age of 24 months.

Histiocytoses in children: analysis of 120 cases and the bone marrow findings in infection-induced hemophagocytic syndrome vs malignant histiocytosis.

Retrospective analysis of childhood histiocytoses treated at the Department of Pediatrics, Ramathibodi Hospital from May 1970 till June 30, 1992 to verify the prevalence according to the recent classification, course and prognosis was conducted. Among 120 cases, 54 were Class I or Langerhan Cell Histiocytosis (LCH, previously called Histiocytosis-X). Nineteen cases were Class II: Infection-Associated Hemophagocytic Syndrome (IAHS) and Sinus Histiocytosis. Forty-seven cases were class III which included acute monocytic leukemia, juvenile CML; malignant histiocytosis, HMR, and histiocytic lymphoma. Excellent prognosis (cure) was seen in all cases of Hand-Schuller Christian Disease, eosinophilic granuloma, sinus histiocytosis with massive lymphadenopathy and many cases of Class II (except IAHS). The worse prognosis (100% mortality rate) was seen in HMR and juvenile CML. The intermediate prognosis (50%, 54%, 58.8% and 66.7% mortality rate) was seen in MH, HL, LSD and IAHS respectively. To differentiate between IAHS and MH/HMR, the prominent bone marrow findings in 12 cases of IAHS revealed that every case showed prominent hemophagocytosis by the promono-histiocytes/histiocytes, the maximal total erythroblasts (TE) were only 7.5 per cent except for 3 cases; in which one case with agranulocytosis from co-trimoxazole had 84 per cent erythroid cells, one case with prior co-trimoxazole treatment had 37 per cent TE, the last one had 40 per cent TE with massive GI bleeding while in the recovery stage of DHF. All 5 cases of HMR had prominent hemophagocytosis and increased TE (> 22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Transmission of HIV infection by seronegative blood in Thailand.

In Thailand, the prevalence of HIV infection in the general population and in donor blood (DB) has sharply increased since 1987. The HIV seropositive rate in DB was increased from 0.0065 per cent in 1987 to 0.95 per cent in 1993 (150 times in 6 years). Heterosexual transmission is the major route of spreading. Therefore, HIV seronegative blood (SNB) poses significant hazard to the recipients because of the risk of viraemia during the window period of early HIV infection. In Thailand HIV Ab screening in all units of blood was started in 1987 and was compulsory nationwide in early 1989. Donor self exclusion (DSE) has been implemented since 1990. It is not fully effective in the prevention of transfusion associated AIDS (TAA) because of many limiting factors. However, DSE should be promoted to practice in every blood bank particularly those that can not do HIV Ag screening. During 1990-1992, there were 30 reported cases of TAA by SNB. The study of risk figure (HIV Ag positive-neutralization with HIV Ab negative) in DB was 1:3,400 and 1:10,000 in two reports in 1991. Under all these circumstances, the national AIDS committee has documented the policy to do HIV Ag screening in every unit of blood from August 1991 and allocated a 10 million baht budget (year 1992) for Ag testing. Several hospitals and NBC reported the risk figures which varied from 1:3,400 to 1:25,000. A certain amount of blood is processed to 2-4 blood components given to 2-4 patients which will increase the number of TAA by SNB.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy in patients with retinoblastoma.

Chemotherapy composed of vincristine, cyclophosphamide, procarbazine and intrathecal thiotepa/methotrexate (in the indicated ones) were given for 1.5 years in the doubtful and very unfavorable (Reese-Ellsworth classification) cases of retinoblastoma. There were 58 new cases treated at the Department of Ophthalmology and the Department of Pediatrics, Ramathibodi Hospital from October 1, 1985 to December 31, 1991. Eight cases had refused the surgery prior to admission. Nine cases were not given chemotherapy due to the very advanced cases and refusal. Forty-nine cases received chemotherapy. Eighteen cases were not followed. Among 31 evaluable cases, three cases had progression of the disease. Twenty-eight cases (90%) were clinically well 2 months-6 years after discontinuation of chemotherapy. The good result could be attributable to spontaneous regression (minimal percentage), surgery, radiation therapy or chemotherapy. However, obvious chemotherapeutic effects were seen in some cases. Even though 28 cases seemed to have good result including three of the 8 cases who had refused surgery before admission, we should stress that retinoblastoma is a curable disease provided that early diagnosis and treatment are rendered. Ophthalmologic examination in first degree relatives should be done in the bilaterally involved cases.

Surgical orthopedic correction of hemophilic hemarthrosis at Ramathibodi Hospital.

During 1982-1992, 15 major surgical orthopedic correction (SOC) were performed in 12 hemophiliacs. There were 11 synovectomy, 2 osteotomy, 1 currettage and suture wound, 1 release of multiple joint contracture and 1 removal of pseudotumour. During 1982-1989, frozen cryoprecipitate was entirely used for replacement therapy in 5 cases who had 7 SOC. During 1990-1992, 7 cases received SOC by using factor VIII concentrate (Emoclot or Profilate) alone or combined with cryoprecipitate in 8 SOC. Multiple surgical procedures could be performed by using factor VIII concentrates. The orthopedist could operate 3 joints in one setting ie right knee, left knee and right middle finger. There are many advantages of factor VIII concentrates over those of cryoprecipitate, especially in the aspect of HIV transmission by HIV seronegative blood products. The disadvantage is the extremely high cost of factor concentrates.

Response of hemophilia A with bleeding to fresh dry plasma.

Fresh dry plasma (FDP) is a lyophilized form of fresh frozen plasma (FFP) which can be stored at 4 degrees C for one year. One bottle of FDP is prepared from 220 ml of FFP and contains FVIII: C 0.75 +/- 0.3 U/ml (mean +/- 1 SD). This study describes the clinical and laboratory response in 7 severe and 4 moderate hemophilia A patients. The age ranged from 7-17 years (mean +/- SD = 11.7 +/- 2.9 years). Either 12.4 ml/kg. FDP or 12.2 ml/kg FFP was transfused to the patients when they had bleeding episodes such as hemarthrosis, hematoma. 16 episodes of FDP and 12 episodes of FFP transfusion were studied. The bleeding could be effectively controlled by FDP or FFP except one patient who had physical therapy at 8 hours post FDP transfusion. The increment of FVIII:C was 14.1 +/- 5.3% at 30 minutes after FDP transfusion and 12.1 +/- 3.7% at 30 minutes after FFP transfusion. The recovery rate was 83.2 +/- 32.6% in FDP and 65.3 +/- 22.7% in FFP transfusion. The FVIII:C was decreased to 78.9 +/- 12.3%, 55.6 +/- 13% and 16.3% of the initial level at 2, 8, 24 hours after FDP transfusion respectively which were not statistically significantly different from FFP transfusion. No serious complication was found. FDP will replace FFP for the treatment of coagulation disorders such as hemophilia A. It is an useful alternative therapy which can be provided to the hemophiliac patients in the rural area in developing countries.

Pulmonary and platelet function in mild form of Hb H disease.

Pulmonary function abnormality, arterial hypoxemia and platelet hyperaggregation were commonly seen in severe or moderately severe thalassemic patients. In previous studies, these abnormalities were found in beta-thalassemia, beta-thalassemia/Hb E disease and Hb H disease in 62, 40 and 52%, respectively. However these functional abnormalities in mild form of Hb H disease have not yet been reported. Pulmonary function test by using standard spirometry, platelet aggregation and arterial blood gases were performed in 23 children with mild form of Hb H disease, whose age ranged from 6-18 years (average 11 years), and hematocrit status was 30-40%. Mild to moderate degree of restrictive lung disorder was found in 48% of these patients, 5% had mild platelet hyperaggregation and none of these had arterial hypoxemia. This study showed that a pulmonary function defect was noted as one significant finding in thalassemic patients, being noted even in the very mild form and early age of life. This information will lead to further exploration of the pathogenesis of pulmonary function defects as well as their role is the patients' future health and prognosis.

HIV seroconversion in Thai hemophiliacs up to 1991.

In Thailand, the anti-HIV screening in the donor blood was started in 1987 and was compulsory nationwide in February 1989. Sixty-six hemophilia A and 10 hemophilia B patients who received approximately six million units of factor VIII and IX in the form of fresh frozen plasma, frozen cryoprecipitate, cryoprecipitate removed plasma, fresh dry plasma and factor concentrate during 1976 to 1991 were tested for anti-HIV since 1987. The age ranged from 1-39 year (mean +/- SD = 15 +/- 7.3). The anti-HIV test was performed by ELISA and/or gel agglutination and confirmed by Western blot analysis. The patients would be checked 1-2 times per year and as necessary. A total of 174 tests for the first, second, third, fourth, fifth and sixth tests were studied in 76, 49, 27, 14, 5 and 3 patients respectively during 1987 to 1991. The prevalence of HIV seroconversion in the year 1987, 1988, 1989, 1990 and 1991 was 2.2% (1/45), 1.9% (1/53), 1.6% (1/63), 1.5% (1/67) and 3.9% (3/76) respectively. Three HIV seroconversion were found in the first, fourth and fifth anti-HIV test in 3 hemophilia A patients who received massive infusion of blood components during orthopedic corrective surgery. One case of HIV seroconversion found in 1987 was transmitted by HIV unscreened blood while 2 cases in 1991 by anti-HIV seronegative blood whose donors were in the window period of HIV infection. The prevalence of HIV seroconversion in Thai hemophiliacs is much lower than those in western countries.(ABSTRACT TRUNCATED AT 250 WORDS)

Developing and maintaining the hemophilia program in Thailand.

Developing of the hemophilia program in Thailand during 1978-1990 has been achieved step by step as follow: 1. In 1978, organizing a series of scientific conferences to motivate and recruit expert teams and to have support from the health authority. 2. In 1978, a national survey of hemophilia which showed an incidence of 1:13,000 of population. 3. Training medical and paramedical personnel during 1973-1992. 4. In 1980, establishment of the National Hemophilia Society. 5. Improvement of blood bank and blood product supported by National Blood Center, Red Cross Society during 1960-1992. 6. In 1981, submitting hemophilia program to the 5th National Health Developmental Plan for 1982-1986. 7. Establishment of a nationwide hemophilia care program by integration with the national health care system. 8. In 1979, starting a home care program and initiation of comprehensive hemophilia care. 9. In 1982, promotion of comprehensive hemophilia care surgical orthopedic correction. 10. Promotion of local manufacture of equipment, reagents, therapeutic material and modification of technology. 11. In 1987, carrier detection. 12. In 1990, laboratory set up for prenatal diagnosis. The future plan is described for the years 1992-2000.

Risk of transfusion associated AIDS by seronegative blood in Thailand: a multicenter report.

Prevention of transfusion associated AIDS (TAA) in Thailand began in 1986 when the HIV infection started to be sharply increased among the general population. The retrospective anti-HIV screening in various blood donor populations by The National Blood Center (NBC) revealed a seroconverted prisoner. Then the use of prisoners, prisoners' blood was not recommended from 1986. In April 1987, the first case of TAA was disclosed. Five months later, anti-HIV screening in all units of blood was firstly introduced at Ramathibodi Hospital (RH) and NBC. From 1989, anti-HIV screening in all units of blood is mandatory nationwide by Ministry of Public Health. Despite the anti-HIV screening, TAA cases transmitted by seronegative blood were gradually reported. Among many Medical Centers, there were 9 and 18 cases of TAA recorded from Chiang Mai and Bangkok areas respectively, since 1985. In addition, several new seroconverters were observed among voluntary blood donors. All of this evidence indicates the existence of blood donation during the early stage of infection, the so-called "window period". At present, HIV-P24 antigen ELISA seems to be the only available technique for mass screening. In 1990, NBC successfully performed a retrospective study on HIV-Ag ELISA screening by obtaining the prevalence of 1/10,000 units of blood. At the same period of time, in RH prospective study, a unit of blood with HIV-Ag only was detected when 3432 units of blood were screened. The HIV-Ag ELISA screening was then performed on every unit of blood routinely since Aug 12, 1991 at RH.(ABSTRACT TRUNCATED AT 250 WORDS)