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.

Disarticulation of a knee joint in a haemophiliac with high inhibitor titre.

Disarticulation of a knee joint in an 8-year-old haemophilia A patient with high inhibitor of 3450 Bethesda units (BU) is described. He had an infected compound fracture of the tibia and fibula. Surgery was successfully performed after extensive plasma exchange; administration of immunosuppressive agents such as cyclophosphamide, methylprednisolone, intravenous immunoglobulin and cyclosporine were combined with a loading dose of 100 units kg(-1) of factor VIII concentrate, followed by continuous infusion of 16 units kg(-1) h(-1) of factor VIII in the form of factor VIII concentrate and cryoprecipitate for 7 days and decreased to 8 units kg(-1) h(-1) in the form of cryoprecipitate for 19 more days. During the 1st to 7th post-operative days, the lowest factor VIII inhibitor was 18 BU and the factor VIII level ranged from < 1-2.1 IU dL(-1) . On the 9th and 13th post-operative day, although the inhibitor rose to 330 and 2700 BU, respectively, there was no serious bleeding. The suture was removed on the 21st post-operative day. The inhibitor spontaneously decreased to 550, 232 and 14 BU at 1, 7 and 10 months, respectively.

DNA polymorphisms for carrier detection of hemophilia in Thailand.

The assessment of carrier state based on the pedigree and laboratory testing in 55 females from 34 Thai hemophilia families (24 affected by hemophilia A, 10 by hemophilia B) was studied. The laboratory testing included phenotypic analysis (FVIII:C/vWF: Ag ratio, FIX:C) and two types of DNA polymorphisms, restriction fragment length polymorphisms (RFLP) and variable number tandem repeats (VNTR) in/and close to the factor VIII genes (Bcl I, Xba I RFLP, St 14 VNTR) and factor IX genes (Mse I, Dde I RFLP). Fifteen out of seventeen (88%) obligate hemophilia A carriers and one out of five (20%) obligate hemophilia B carriers were diagnosed by phenotypic analysis. All hemophilia A carriers were informative for at least one polymorphism (Bcl I, Xba I or St 14) while 42% of hemophilia B carriers were informative for Mse I RFLP only. DNA polymorphism analysis has advantage over phenotypic analysis since it generally gives an absolute diagnosis when informative. Most DNA polymorphism analyses are performed by PCR technique which is a simple, inexpensive and quick procedure. However, it is limited by non-informativeness and high incidence of new mutations.

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)

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.

Response of patients with bleeding disorder to DDAVP administration.

DDAVP has been shown to provide hemostasis in patients with bleeding disorder. Thirty-one episodes of intravenous DDAVP administration (0.3-0.4 microgram/kg) in 22 patients with bleeding disorder were studied. There were 13 patients with hemophilia A, 1 with type I vWD and 8 with inherited and acquired platelet dysfunction. The age ranged from 2.3-26 yrs (mean +/- SD = 10 +/- 4.8). None of the 3 severe hemophilia A patients responded to the treatment. Two out of five episodes in 4 moderate hemophilia A patients responded clinically and had minute increments of F VIII:C. Ten out of eleven episodes (91%) in 6 mild hemophilia A patients had good responses. The dental procedures for these patients were successfully performed without blood component transfusion. The increments of F VIII:C ranged from 1.5-6.8 folds over the baseline levels (mean +/- SD = 2.5 +/- 1.4). In addition, two episodes of epistaxis in a vWD patient responded excellently and one dental procedure was successfully performed by giving DDAVP. The increments of F VIII:C and vWF:Ag ranged from 2.8-12.5 and 2.9-8 fold over the baseline levels respectively. The prolonged bleeding times were shorten to 6.5-7 minutes. Only three out of eight episodes in 8 inherited and acquired platelet dysfunction patients showed temporary responses. The bleeding time responses did not correlate with in vitro platelet aggregation.

Immunoglobulins in acquired platelet dysfunction with eosinophilia.

Acquired platelet dysfunction with eosinophilia (APDE) is acquired bleeding diathesis associated with platelet dysfunction causing prolonged bleeding time. Most of them had eosinophilia. Various reports of the isolated cases had normal level of immunoglobulins but few had increased IgE. This report is different from others in that among 41 cases of APDE, it was found that most of them had normal levels of IgG, IgA, IgE but there was increased IgM in 95.1% of the cases. Increased in IgE was noticed in 7/24 cases (29.2%) and only half (3/6 cases) corresponded with eosinophilia.

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.

Platelet counts in thalassemic children before and after splenectomy.

Even though thrombotic risks in thalassemia patients from standpoints of platelet dysfunction and coagulation factors are controversial, they are in favor of thrombosis due to thrombocytosis. From the study of 74 cases of thalassemia in children, marked thrombocytosis occurred during day 8 to 4 months during which one should be aware of the thrombosis. However, none of thalassemia children had acute thrombosis even at platelet counts of 1.6 million/microliters.

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.

Standardization of platelet aggregation test in normal Thai adults.

Platelet aggregation test was assessed by the turbidimetric method in 52 normal Thai adults consisting of 24 males and 28 females with ages ranging from 20 to 50 years. The aggregating agents used were adenosine diphosphate (ADP), adrenaline and collagen. It was found that the ranges of threshold concentration of ADP, adrenaline and collagen which gave maximal induction of platelet aggregation were 5-10 microM, 2.5-10 microM and 0.14-0.28 mg/mL, respectively. Collagen at the above concentration, showed lag phase within 2 minutes. This corresponds to that described in the reference method. Moreover, when induced by ADP and adrenaline 53-65 per cent and 81-87 per cent of the subjects, respectively, showed biphasic curve. The above concentration of ADP, adrenaline and collagen are suitable for the study of platelet aggregation in normal Thai adults.

Exchange transfusion and pulse steroid therapy in a hemophiliac with inhibitor.

In Thailand, the management of bleeding in hemophiliacs with inhibitor is still a challenging aspect. The source of Factor VIII is locally prepared fresh frozen plasma and cryoprecipitate. The Factor VIII concentrate and other commercial blood products are not available because of the remarkably high price. Successful management of bleeding in a 3-year-old hemophiliac boy with moderate inhibitor level (11.82 BU) was reported. He had active bleeding from a 1 cm size cut wound at upper gingivo-buccal fold and did not respond to local measures and supportive treatment. He received exchange transfusion, intravenous cyclophosphamide and high dosage of cryoprecipitate. The bleeding stopped and the inhibitor declined to 2.6 BU. A week later, the bleeding recurred with an anamnestic response of inhibitor to 5 BU. The second exchange transfusion and methylprednisolone as pulse steroid therapy were given daily for 3 days. No cryoprecipitate was infused. The bleeding gradually stopped within 48 hours and the inhibitor level declined to 3.2 BU which was still at low level for at least 2 months. Exchange transfusion and methylprednisolone as pulse steroid therapy may be an alternative treatment for controlling bleeding in a hemophiliac with moderate inhibitor level in countries where a high concentrate of Factor VIII or other blood products are not available. It is practical, simple, effective and of low cost.

Vitamin K prophylaxis in the neonates by oral route with different dosages.

This paper evaluated the effect of VKP in the neonates by oral route with different dosages compared to the standard parenteral route giving a single dose at birth. Two hundred and thirty-six healthy, breast-fed infants were divided into 4 groups receiving vitamin K1 1 mg intramuscularly and 2, 3, 5 mg orally during 2-4 hours after birth. The vitamin K dependent clotting factors were measured by the thrombotest at the age of 2 weeks and 4-6 weeks. The result showed no statistical differences among these 4 groups regarding the mean prothrombin complex level and the number of PC deficient subjects. Vitamin K prophylaxis in the newborn babies by 2 mg oral route would be benefit and can be applied routinely as well as 1 mg parenteral route to prevent both HDN and APCD syndrome particularly in breast fed infants. The routine practice of giving vitamin K1 prophylaxis 2 mg orally or 0.5-1 mg intramuscularly should be recommended to all newborn infants. Giving VKP by oral route is practical for developing countries because of simple way of administration, low cost, low toxicity, as well as high efficacy.

Fresh dried plasma: a solution for the shortage of blood products in developing countries.

The availability of blood products for replacement therapy of hemophilia and allied disorders is still a formidable problem in most developing countries which consist of 80% of the world population. Fresh dried plasma (FDP) is a lyophilized form of fresh frozen plasma which can be stored at 4 degrees C, whereas fresh frozen plasma must be stored at -20 degrees C. A large-scale production of FDP from single units of fresh frozen plasma was achieved by the National Red Cross Blood Center in Thailand. This paper describes the method of preparation, biochemical and blood coagulation properties of FDP during one-year storage as well as its clinical usefulness. A batch of 179 bottles of FDP stored at 4 degrees C for one week, 3, 6, 9 and 12 months was studied in order to determine the biochemical and blood coagulation parameters. FDP has pH higher than that of fresh frozen plasma, but its value is within the safety range for infusion. Electrolyte and protein levels were comparable with those of fresh frozen plasma. Coagulant activities of factors I, II, V, VII, VIII, IX and X were about 10% lower than those of fresh frozen plasma; however, they are in the acceptable therapeutic range and all were stable during storage at 4 degrees C for up to one year. Over 4,000 bottles of FDP were used with good clinical and laboratory response and no series side effects were observed in the treatment of bleeding in blood coagulation disorders and home care therapy of hemophilia.

Hemostatic derangement in dengue haemorrhagic fever.

Forty children, aged 1/2-14 years, with serologically proven dengue haemorrhagic fever were daily studied for hemostatic tests. There were 4, 20 and 16 cases of grade I, II III respectively. Hemostatic derangements in DHF is a multifactorial mechanism. Vasculopathy, thrombocytopenia, platelet dysfunction were found in most cases. Mild to moderate degree of prothrombin complex deficiency was observed in 15% and 50% of grade II and grade III respectively while laboratory evidence of consumptive coagulopathy was noted in 30% of shock cases and 10% of non-shock cases. Hypofibrinogenemia and increased PTT are commonly seen in grade III reflect the presence of stimulation of intrinsic coagulation pathway probably from immunologic reaction. Frank DIC is very rarely observed. FDP is slightly increased but not as high as in classical DIC. Further study on the role of platelet-endothelial interaction should be elucidated including the efficient management to stop bleeding in severe shock cases.

Cardiac study in thalassemic children.

Cardiac function was studied in 54 thalassemic children, aged 3 to 18 years. Abnormalities were found by echocardiography in 58%, by electrocardiography in 15%, and by chest film cardiomegaly in 24%. There was a correlation between the severity of anemia and the degree of cardiomegaly.