Adequate Transfusion Research Articles

Low Bone Mineral Density in Adolescents with β‐Thalassemia

The pervasiveness of low bone mass (LBM) in beta-thalassemia (Thal) patients (pts) is escalating as the average life expectancy of these pts increases. Adolescence is a period of substantial bone accrual, which is crucial for future bone strength. Studies of LBM are prevalent among adults with Thal. However, limited information exists about bone accrual and LBM in adolescents with the disease. Thirty-one pts with beta-Thal (26 Thal major [TM], 5 Thal intermedia [TI]), aged 9-20 years (mean: 15.3 years), 14 males and 17 females, underwent measurement of spinal bone mineral density (BMD) by DEXA (Lunar, Prodigy). Height, weight, body mass index, and Tanner stage were assessed at the time of the BMD measurement. A total of 16.1% of the patients had normal bone mass (Z > or = -1), 22.6% had reduced bone mass (Z = -1 to -2), and 61.3% had low bone mass (Z < or = -2). BMD Z correlated with height and weight Z scores. Some 53.9% of subjects had normal gonadal function and 46.1% had induced puberty with gonadal steroids. BMD Z significantly worsened with age (P < .0001). However, there was no difference in the LBM prevalence between subjects with normal versus those with induced puberty: BMD Z was -2 or less in 71.4% of subjects with normal puberty versus 66.7% in those with induced puberty. Our results indicate a high prevalence of LBM among adolescents with Thal regardless of adequate transfusion and chelation regimens. Bone accrual was found to be suboptimal in adolescents with normal or induced puberty. Thus, calcium and vitamin D supplementation with antiresorptive therapies should be evaluated in the adolescent Thal pt with close monitoring of growth and sexual development.

Incidence, severity, and management of anemia during concurrent chemoradiation for head and neck cancer

5563 Background: Anemia, causing tumor hypoxia, can reduce the efficacy of radiation therapy (RT), particularly in patients with head and neck cancer (HNC). Low average weekly nadir hemoglobin (AWNH) has been associated with increased cancer recurrence. The incidence, severity, and management of anemia, including the use of erythropoietin or blood transfusion, during concurrent chemoradiation for HNC is unknown. Methods: Medical records of patients with unresectable HNC who were treated with concurrent chemoradiation during 1999–2003 were reviewed. Patients with less than 10% planned radiation dosage, impaired renal function, or cancers of the paranasal sinuses or parotid glands were excluded. Results: Forty-eight patients were included for analyses. Mean age was 59.9 years; 95.6% had stage III or stage IV disease. Mean radiation dose was 65.0 Gy. The incidence of anemia was very high: 70.8% had hemoglobin below 10 g/dl; 91.6% below 12 g/dl; mean nadir hemoglobin was 9.0 g/dl; AWNH was 10.7 g/dl. No patients received erythropoietin during RT. Total episodes of transfusion was 1.8 per patient; 19/48 (39.6%) were transfused at least once. Mean lowest hemoglobin threshold of transfusion was 7.4 g/dl. The first transfusion occurred at about 3.2 weeks since initiation of radiation. Total blood transfused were 3.3 units per patient. Transfused patients had significantly lower hemoglobin at baseline compared with non-transfused counterparts (10.8 vs 12.4 g/dl, p=0.002). Patients who received multiple chemotherapeutic agents concurrently with radiation were more frequently transfused than did patients receiving single-agent platinum (47% vs 10%, p=0.03). Most patients who did not receive transfusion remained anemic at the conclusion of RT; 51% had hemoglobin below 12 g/dl; 86.2% below 10 g/dl. Conclusions: Anemia during concurrent chemoradiation for HNC was prevalent. AWNH was critically low, potentially causing insensitivity to RT. Our patients were mainly managed by transfusion; however, the intensity of transfusion was less than desirable. Further studies using adequate transfusion and/or erythropoietin to improve tumor control are warranted No significant financial relationships to disclose.

Prolonged hematopoietic reconstitution in patients failing previous peripheral blood stem cell collection, transplanted with adequate number of the CD34 cells obtained during bone marrow harvest

6641 Background: According to current EBMT recommendations 2.0 x 106 CD34 positive cells /kg is regarded as adequate transplant material, capable to reconstitute hematopoiesis after high dose chemotherapy. Methods: In our department we routinely use peripheral blood stem cell collection (PBSCC) as a source of a autologous transplant material. During the last 5 years only 37 out of 154 transplanted leukemia and lymphoma patients had an effective BM harvest performed. It was done electively in 10 patients, while the rest failed 1 or 2 previous PBSCC procedures (17 and 10 cases). Those 3 groups were compared with respect to engraftment. Results: In our protocols we most often used Cyclophosphamide, ESHAP or DICEP mobilisation chemotherapy for lymphoma patients and intermediate dose cytarabine for leukemias. BM harvest after the second PBSCC failure was not performed in heavily pretreated patients, beyond the first relapse, or after failing more then 2 upfront lines of chemotherapy. Despite low percentage of CD 34 positive cells in bone marrow before the harvest (0.35% of mononuclear cells, range 0.25 –0.45%) reasonable transplant material was obtained by increasing the harvested volume to 2.5 liters. With adequate transfusion policy the procedure was feasible and safe. Although the CD34 counts were comparable between 3 groups (median 1,9, 1,8, 1,5 for harvested upfront, after failing 1 and 2 PBSCC respectively), engraftment and hematopoietic reconstitution was delayed significantly in the 3-rd group (median 26 days). Conclusions: When considering to perform autologous stem cell transplant in patients failing 2 previous PBSCC procedures, although it is probably possible to obtain adequate numbers of CD34 positive cells during BM harvest one should have in mind the delayed engraftment. This is likely to happen also if the CD34 counts are 2.0 x 106/kg or above. Therefore in our Department we recommend it only for the high risk cases. No significant financial relationships to disclose.

Antibodies to high-frequency antigens may decrease the quality of transfusion support: an observational study.

There is only little information on the transfusion support of patients with antibodies to high-frequency RBC antigens. In cooperation with reference laboratories and transfusion services in Austria, Germany, and Switzerland, the transfusion support provided to hospitalized patients identified as having such antibodies was reviewed during a 20-month period. A total of 52 patients with antibodies to high-frequency antigens were treated in hospitals. Twenty-two of them received 104 units of antigen-negative RBCs. In 23 cases, a deviation from the standard transfusion policy (e.g., transfusion of antigen-incompatible units) occurred. The use of frozen or fresh units varied amongst the different countries but did not affect the rate of deviation from protocol. About 20 percent of all units were supplied internationally. Four antibody specificities, anti-Kpb, anti-Vel, anti-Lub, and anti-Yta, were identified in two-thirds of the patients. This survey indicated that transfusion support was unsatisfactory in about one-third of the hospitalized patients with antibodies to high-frequency antigens. Maintaining a rapidly accessible stock of just four types of rare blood units would ensure adequate transfusion support for most of these patients.

Indications for Prothrombin Complex Concentrates in Massive Transfusions

A major hemorrhagic insult may require massive transfusions to maintain oxygen transport and hemostasis. Thus an adequate transfusion budget must consider losses, patient's blood volume, critical levels of laboratory parameters, replacement rates of coagulation factors from the extravascular space, and the efficacy of blood products. The substitution of large quantities of blood or red cell concentrates can induce and aggravate a complex haemostatic disorder. Some patients develop generalized microvascular bleeding. A transfusion regimen is described, which in our hands can reduce complications of massive transfusion. For hemostatic support, platelet concentrates and fresh frozen plasma are the treatment of choice. Localization and persistence of bleeding, hepatic disease, and vitamin K deficiency due to medication or intestinal malabsorption may require the supplementary use of prothrombin complex concentrates. Furthermore, antithrombin and fibrinogen concentrates may be indispensable.

The hemostatic effect of adequate red cell transfusion in patients with anemia and thrombocytopenia

The hemostatic effect of adequate red cell transfusion in patients with anemia and thrombocytopenia

適合血小板輸血における非溶血性非発熱性副作用と血小板輸血無効の関連性

Two patients had platelet transfusion refractoriness accompanied with non-hemolytic-, and non-febrile-hypersensetivity reactions nevertheless HLA-, and HPA-matched platelets were used. Whether the development of hypersensitivity reactions and refractoriness were associated with HLA or ABO match grade between patient and donor, we estimated corrected count increment at 1-hour posttransfusion (CCI-1hr) after HLA-, and HPA-matched platelet transfusion. The CCI-1hr more than 0.75×104/μl was used to determine adequate transfusion response.Regardless of HLA or ABO match grade, hypersensitivity reactions following HLA-, and HPA-matched platelet transfusion were observed in 14 of 23 transfusions in case 1, and in 6 of 15 transfusions in case 2. When there were any hypersensitivity reactions, adequate transfusion responses were obtained in 4 (29%) of 14 transfusions in case 1, and in 2 (33%) of 6 transfusions in case 2. However, effective increments were observed in most of transfusions (78%, 89%, respectively) when hypersensetivity reactions were not found.Heal et al. hypothesized that antibodies to polymorphic plasma proteins could be involved in platelet transfusion refractoriness by an “innocent bystander” or “immune complex” mechanism, our findings were strongly suggestive of their possibility.

A survey of basic resuscitation knowledge among resident paediatricians.

A telephone questionnaire was undertaken to evaluate the knowledge of resident paediatricians on the subject of the basic resuscitation of the acutely sick child. The questionnaire was targeted at 88 resident paediatricians in hospitals accepting paediatric emergencies in four health regions. Outcome was measured as a correct response to questions based on several emergency scenarios and on the confidence expressed of basic resuscitation knowledge. The subject of emergency management of the child with a compromised upper airway was poorly answered with 40/73 (55%) resident paediatricians suggesting an incorrect endotracheal tube size for an 8 year old child. Fluid management was also deemed unsatisfactory with only 36/73 (49%) providing adequate transfusion secondary to haemorrhagic shock. In addition only 19/73 (26%) mentioned the intraosseous route as a means of obtaining vascular access in a child in extremis. Confidence of the knowledge of basic resuscitation of children was low among resident paediatricians with only 30/73 (41%) expressing confidence and 69/73 (94%) expressing a desire for more formal training in paediatric resuscitation. Resident paediatricians are usually the key personnel in the management of very sick children. This survey demonstrates a low level of basic resuscitation knowledge among resident paediatricians of all grades that must be remedied at a local and national level.

The radiographic appearances following adequate transfusion in beta-thalassaemia.

The main lesions of the skull and hand, observed in a group of hypertransfused beta-thalassaemic patients, are compared with a control group of low-transfused patients. Bony abnormalities reflect the relationship between proliferating bone marrow and bone cortex, and hypertransfusion therapy will prevent development of lesions only if established early in life. If this is done, the diploë in the skull may become normal, overgrowth of facial bone is moderate, pneumatisation of the paranasal sinuses is not completely prevented, and the "hair-brush" pattern may disappear completely. A normal appearance of the hand in adequately treated patients differentiates between prepubertal patients and adults.

Editorial retrospective. Iron loading in thalassemia--five years with the pump.

The more severe forms of β-thalassemia, which are among the commonest single-gene disorders in the world, are particularly distressing, because affected children who receive adequate transfusions grow and develop normally, only to die of cardiac failure secondary to iron loading of the myocardium toward the end of the second decade.1 Although chelating agents, such as deferoxamine, were introduced in the early 1960s to treat iron loading in thalassemia,2 early experiences were disappointing, and their use was largely abandoned. However, in 1974 a small study carried out in London showed that patients with β-thalassemia who had received regular bolus injections of . . .

Surgery of violence. V. Missile wounds of the head and spine.

The patient with a cerebral gunshot wound has a very unstable condition. In Belfast emphasis has been laid on rapid evacuation and on starting resuscitation within a few minutes of injury. Early and adequate transfusion combats shock; controlled ventilation helps limit the rise in intracranial pressure. Intracranial haematomata should be sought by early operation. Operation seldom improves neurological function in missile wounds of the spine.

Surgical management of bleeding gastric and duodenal ulcer—with special reference to indications for operation—

A total of 79 cases with bleeding gastric and / or duodenal ulcers subjected to operation were retrospectively reviewed with special reference to indications for.operation. The results are as follows: (1) The 79 bleeding ulcer cases, sharing 15.6% of all operated patients with gastric and / or duodenal ulcer, consisted of 49 with gastric ulcer, 21 with duodenal ulcer, and 9 with coexisting ulcer. Emergency operations were performed in 20 (25.3%) of the 79 cases; (2) Shock complicated in 31 (39.2%) of the 79 cases revealed its incidence higher in the emergency operation, i.e., in 9 (45%) of the 20 cases; (3) Operative mortality was also higher in rate for the emergency operation cases, 4 deaths (20%) out of 20, than for all bleeding ulcer cases, 7 deaths (8.9%) out of 79 cases. Five of the 7 operative deaths were in patients over 60 years of age; (4) Emergency or elective operation should be finally decided after a careful examination on the patient’s general conditions, paying regard to ages, actual and opssible rebleeding, and coexistent diseases; emergency operation should be considered if adequate transfusion proves unsuccessful in relieving shock or rebleeding.

Glucose phosphate isomerase deficiency with hereditary nonspherocytic hemolytic anemia

Eight children (5 living, 3 deceased) with severe hereditary nonspherocytic hemolytic anemia caused by glucose phosphate isomerase deficiency have been observed in two Kentucky and Indiana families. All affected children were severely anemic in early life. Three deaths occurred in young patients who did not receive adequate transfusions of blood or whose parents refused to permit splenectomy. Splenectomy generally abolishes the requirement for blood transfusion. No patient has required regular transfusion of blood after puberty. Growth and development have been surprisingly normal and no patient has died of infection. The anemia is expressed as an autosomal recessive trait, but the enzyme variant can be detected in hematologically normal heterozygotes. The abnormal isomerase molecule is heat labile and is contained in neutrophils and lymphocytes as well as in erythrocytes.

Perinatal genital hematomas.

The incidence of perinatal genital hematoma formation was one in 926 deliveries in this series. Primigravidas, toxemic patients, patients with multiple pregnancy, vulvovaginal varicosities and those requiring instrument deliveries were more prone to this complication. Large baby, prolonged second stage of labor and persistent occipitoposterior position were not associated with an increased incidence of hematoma formation. In this series, 87% occurred after episiotomy or a perineal laceration was sutured. Proper suturing, early diagnosis and therapy, including adequate transfusion, are stressed to reduce morbidity from this unfortunate complication.

COMMENTS ON GRAHAM ET AL'S ARTICLE IN DECEMBER 1968 ISSUE-Reply

To the Editor .—I would have no particular objection to the use of four intravenous cannulas provided starting of the extra two does not delay surgery and provided that they are sufficiently watched to avoid overloading the patient. However, we have found two intravenous catheters to be sufficient in most cases. This is related, in part, to our method of handling the aneurysm patient. Transfusion of blood is not begun in most cases until the patient is ready for anesthesia and incision, since transfusion before this time may result in recurrence of or increase in bleeding. Following incision, aortic control can be gained within one minute with the hand or an instrument. No further surgery is done at this time until adequate transfusion has been done and an adequate blood pressure attained. Subsequently, with control of the aorta, dissection can be done and a clamp applied. Most patients with ruptured

Hypotension accompanying ECG changes in two uremic patients with severe hypocalcemia

Three observations in 2 uremic patients with severe hypocalcemia are described. 1. 1. Besides prolongation of the Q-T interval, severe hypotension was found. 2. 2. During intravenous administration of calcium the blood pressure rose, and the Q-T interval was normalized concomitant with the increase of the concentration of plasma calcium to its normal level; when in the second patient the concentration of Ca again diminished, hypotension and prolongation of the Q-T interval reappeared. 3. 3. In the first patient a triple rhythm was present during hypocalcemia, but disappeared during administration of Ca. A flaccid paresis of short duration of the lower limbs existed, but also disappeared completely during administration of Ca. Chvostek's sign was consistently negative. 4. 4. The conclusion is that in these cases, hypocalcemia was responsible for the hypotension, probably by decreasing the force of cardiac contraction. The slightly elevated level of potassium found in all three observations may have been a contributory factor. 5. 5. Since others have made similar observations after massive transfusion of citrated blood, and during major operations, the possibility of hypocalcemia should be considered in patients with hypotension refractory to adequate transfusion. The finding of a prolonged Q-T interval due to lengthening of the S-T segment is then of diagnostic importance, since the classic neurological signs of hypocalcemia may be absent.

A Simple One-Stage Method for the Assay of Antihemophilic a Factor with a Comment on the Plasma Level of this Factor in Hemophilia A

A simple and reliable method for the assay of antihemophilic A factor is greatly needed both for diagnostic purposes and for the guidance of adequate transfusion therapy in hemophilia A. The great number of methods proposed reflects the difficulty in arranging a test system which combines accuracy and reproducibility with simplicity and quick performance. The thromboplastin generation test (Biggs & Douglas 1953) provided a useful method for the differentiation between hemophilia h and other blood clotting anomalies. The various modifications of this method (Biggs, Eveling & Richards 1955 ; Pitney 1956; Biggs 1957) are probably among the most reliable and accurate tests for the quantitative assay of antihemophilic A factor. Unfortunately, however, they are all relatively complicated and time-consuming. Modifications of the prothrombin consumption test (Graham, Collins, Godwin & Brinkhous 1951; Quick & Hussey 1956) and of the thrombin generation test (Wolf 1956), which all seem to give sensitive assay procedures, are also rather laborious and time-consuming.

Treatment of haemorrhage from peptic ulcer by continuous intragastric milk drip.

fciaily in the present century, Lenhartz (1904) advised feeding with milk and raw eggs from the first day. How ever, many hospitals in this country continued to employ initial starvation until Meulengracht (1934) introduced a further plea for early generous feeding. It seems doubtful, he wrote, whether it be particularly expedient to pick out for weakening dietetic measures the very point of time when a patient has lost a con siderable amount of blood and is rather poorly. The 'thirties saw other important therapeutic advances : Marriott and Kekwick (1935) demonstrated the impor tance of adequate transfusion ; Finsterer (1933) made, and Gordon-Taylor (1935) successfully defended, the case for early operation in patients with established ulc?ration and severe haemorrhage, pointing to lower mortalities if the gastrectomy was performed in the first 48 hours. Those tempted to question whether this advice is applicable now the patient has adequate food and transfusion during the first two days should note that Tanner (1951) has proposed, and is at present employing, a return to the Finsterer regime. Recent authors? such as Ogilvie et al. (1952), have stressed the importance of medico-surgical team-work in the manage ment of bleeding ulcers. With what appeared to be steady therapeutic advances in the first half of this century one would have expected a comparable decline in mortality. However, there was a rise during the first quarter of the century. The factors which caused this and led to subsequent confusion were stated by A very Jones (1947) in the Goulstonian Lec tures. Those wishing to learn the pitfalls of drawing conclusions from published mortalities are referred to these lectures.

POST-TRAUMATIC RENAL INJURY

Early and adequate transfusion, prevention of infection and improved supportive measures are responsible for the survival of an untold number of casualties whose injuries would formerly have been rapidly fatal. But the very survival of persons seriously injured raises new problems in traumatotherapy, among which anuria assumes increasing significance. This report summarizes clinically relevant observations made during an experimental study of post-traumatic renal injury. The effects of trauma on renal function vary widely, according to the nature, severity and duration of the injury. Hemorrhage which does not cause prolonged hypotension usually results in temporary anuria, which is corrected by transfusion and which has no more significant sequel than the transitory appearance in the urine of casts, protein and red blood cells. Prolonged shock from hemorrhage or skeletal trauma may be followed by oliguria or anuria which does not respond to transfusion and culminates in uremia, although no specific renal lesion

Treatment of bleeding in the first and third trimesters of pregnancy

1.1. Bleeding during the first third of pregnancy occurred in bout 10 per cent of all obstetric patients admitted to the New York Lying-in Hospital in the past ten-year period.2.2. This bleeding was due mainly to abortion, complete or incomplete, or to threatened abortion.3.3. Other causes of bleeding were: (a) ectopic pregnancy, (b) hydatidiform mole, (c) erosion of cervix or polyps, (d) chorionepithelioma, (e) carcinoma of the cervix.4.4. The proper treatment for patients with bleeding of the first trimester includes hospitalization, bed rest, blood grouping and matching, and physical examination. Observation for a varying period of time is essential in threatened as well as incomplete abortion. Conservative treatment is recommended in the presence of potential or actual infection of the uterine eavity.5.5. Vitamin E and perhaps progesterone are of value in certain cases of threatened abortion. A low basal metabolic rate must be corrected with proper thyroid therapy.6.6. Dilatation and curettage are performed on the basis of continued or excessive bleeding in incomplete or threatened abortion. The Aschheim-Zondek test is of value in these eases.7.7. Curettage is not performed in infected patients. Hemorrhage in these patients may necessitate evacuation of the uterus with the finger or ovum forceps, used with utmost care.8.8. The treatment for ectopic pregnancy is laparotomy with adequate transfusion.9.9. Cervical erosion, polyps, and carcinoma of the cervix, although infrequent causes of bleeding, must be ruled out by examination. If these are present, the appropriate therapy is applied. In carcinoma of the cervix, early treatment is essential and must be carried out irrespective of the gestation.10.10. Bleeding of the last third of pregnancy is due usually to placenta previa or premature separation of the placenta.11.11. The incidence of placenta previa was 0.52 per cent and of premature separation of the normally implanted placenta 0.36 per cent.12.12. All patients with bleeding in the latter third of pregnancy must be hospitalized and a suitable donor or blood from a blood bank procured immediately.13.13. In all these cases, except those in shock or with excessive bleeding, an observation period of several days is indicated.14.14. Our treatment in placenta previa is conservative, including the introduction of a bag in certain cases, except in central placenta previa, or in partial placenta previa with a fairly closed, long, or rigid cervix. In this latter group cesarean section becomes the procedure of choice.15.15. In premature separation of the normally implanted placenta, cesarean section is performed unless the cervix is partially dilated and early vaginal delivery may be expected.16.16. Where cesarean section is performed for premature separation of the placenta, hysterectomy should be done only in those cases where great disintegration of the muscular wall of the uterus is present and the organ does not contract satisfactorily.17.17. With the treatment as outlined above our maternal mortality from placenta previa was 0.75 per cent and from premature separation of the placenta 3.2 per cent. The maternal mortality in all patients with antepartum bleeding during the last trimester of pregnancy, including low implantation and undiagnosed placenta previa, was 0.71 per cent.18.18. We do not advocate wider use of cesarean section in placenta previa on the basis that it will increase the number of living infants, for cesarean section still carries an appreciable maternal mortality due to infection and hemorrhage.