Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study.

BACKGROUND: Recent reports have suggested an association of atherosclerosis with risk of venous thrombosis. OBJECTIVE: To confirm whether subclinical atherosclerosis is a risk factor for venous thrombosis (VT) among men and women age 65 and older. METHODS: Participants of the Cardiovascular Health Study (n = 4,108) without baseline clinical cardiovascular disease, anticoagulant use or previous VT were followed for a median of 11.7 years after non-invasive assessment of subclinical atherosclerosis using carotid ultrasound (intima-media thickness and presence of plaques), ankle-brachial blood pressure index and electrocardiogram. Each event was classified as idiopathic or secondary. We used Cox proportional hazards regression to estimate the relative risk of overall and idiopathic VT for individuals with and without baseline subclinical atherosclerosis. RESULTS: There were 133 first time VT events. No subclinical atherosclerosis measures were associated with increased risk of overall or idiopathic VT. The adjusted relative risks of overall and idiopathic VT for presence of any type of subclinical disease were 0.60 (95% confidence interval 0.39-0.91) and 0.32 (0.18-0.59), respectively. Most of this association was explained by an inverse association of high-risk carotid plaques (prevalent in 54% of those at risk) with VT. CONCLUSION: Non-invasively measured subclinical atherosclerosis was not associated with increased risk of overall or idiopathic VT in this observational study. Carotid plaques and arterial events during follow up were inversely associated, a finding that requires further study.

Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism.

BACKGROUND: Whether atherosclerotic disease predisposes to venous thrombosis is uncertain. OBJECTIVE: To determine whether subclinical atherosclerosis, manifested as increased carotid intima-media thickness (IMT) or presence of carotid plaque, is associated with increased incidence of venous thromboembolism (VTE). PATIENTS AND METHODS: The Atherosclerosis Risk in Communities study is a prospective cohort of adults aged 45-64 years, examined at baseline (1987-89) and followed for cardiovascular events. Bilateral carotid ultrasound for IMT measurements was done at baseline for portions of the common and internal carotid arteries, and carotid bifurcation and also to detect the presence of carotid plaque. Exclusion criteria included baseline anticoagulant use, history of coronary heart disease, stroke, or VTE, and incomplete data. First VTE during follow-up was validated using abstracted medical records. RESULTS: Among 13,081 individuals followed for a mean of 12.5 years, 225 first VTE events were identified. Unadjusted hazard ratios (HR) (95% CI) of VTE across quartiles of baseline IMT were 1.0, 1.16 (0.77-1.75), 1.64 (1.12-2.40), and 1.52 (1.03-2.25). However, this association disappeared after adjustment for age, sex, and ethnicity (HRs: 1.0, 1.06, 1.40, and 1.18). Further adjustment for body mass index and diabetes weakened the relative risks even further. Presence of carotid plaque at baseline also was not associated with VTE occurrence; adjusted HR = 0.97, 95% CI = 0.72-1.29. CONCLUSION: Increased carotid IMT or presence of carotid plaque was not associated with an increased incidence of VTE in this middle-aged cohort, suggesting subclinical atherosclerosis itself is not a VTE risk factor.

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system.

We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m2/day, x 4 days; thiotepa 300 mg/m2/day, x 3 days; and carboplatin approximately 500 mg/m2/day, x 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cis-retinoic acid, +/-oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.+/-8%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day +9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.

The effect of preoperative donation of autologous blood on deep-vein thrombosis after total hip arthroplasty.

We have assessed the effect of the donation of autologous blood and the preoperative level of haemoglobin on the prevalence of postoperative thromboembolism in 2043 patients who had a total hip arthroplasty. The level of haemoglobin was determined seven to ten days before surgery and all patients had venography of the operated leg on the fifth postoperative day. The number of patients who had donated autologous blood (1037) was similar to that who had not (1006). A significant decrease in the incidence of deep-vein thrombosis (DVT) was noted in those who had donated blood preoperatively (9.0%) compared with those who had not (13.5%) (p = 0.003). For all patients, the lower the preoperative level of haemoglobin the less likely it was that a postoperative DVT would develop. Of those who had donated blood, 0.3% developed a postoperative pulmonary embolism compared with 0.7% in those who had not, but this difference was not statistically significant. No significant difference was found in the requirements for transfusion between the two groups.

Removal of ABO-incompatible red cells from lymphocytapheresis and granulocytapheresis components before transfusion.

BACKGROUND: The collection of allogeneic lymphocytapheresis and granulocytapheresis components containing significant volumes of ABO-incompatible red cells is sometimes necessary. STUDY DESIGN AND METHODS: Twenty-nine ABO-incompatible lymphocytapheresis components collected for transfusion to three patients and 11 ABO-incompatible granulocytapheresis components collected for transfusion to five patients were depleted of red cells by gravity sedimentation aided by the addition of hetastarch solution. The efficacy of red cell depletion and white cell retention and the complications of transfusion were analyzed. RESULTS: Lymphocytapheresis components contained 82 +/- 13 percent of the original white cells and 5 +/- 3 mL of red cells after depletion; however, for those components containing < 70 mL of red cells before depletion (n = 12), white cell recovery was 92 +/- 5 percent. After depletion, granulocytapheresis components contained 96 +/- 3 percent of the original white cells and 6 +/- 2 mL of red cells. No clinical or laboratory evidence of hemolysis was observed after the transfusion of any leukapheresis component. CONCLUSION: Red cells can be effectively removed from leukacytapheresis components by a simple gravity sedimentation technique with added hetastarch. This allows safe transfusion of ABO-incompatible components.

Beneficial impact of peripheral blood progenitor cells in patients with metastatic breast cancer treated with high-dose chemotherapy plus granulocyte-macrophage colony-stimulating factor. A randomized trial.

BACKGROUND: This study compared the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with peripheral blood-derived hematopoietic progenitor cells (PBP) as support for patients receiving high-dose chemotherapy and assessed the adequacy of these strategies as alternatives to autologous bone marrow rescue. METHODS: The authors studied patients with metastatic breast carcinoma who had a major response to conventional chemotherapy or had achieved a complete remission by surgical resection of all known metastases. They were treated with carboplatin 1500 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide 5.0 g/m2. Before this high-dose chemotherapy, the patients had been randomly assigned to one of two hematopoietic support strategies: GM-CSF alone (Group 1) or GM-CSF-primed PBP and GM-CSF (Group 2). Autologous bone marrow was harvested from all patients for use only in the event of persistent pancytopenia with marrow aplasia on day 15. RESULTS: A total of 18 patients were treated. Randomization was halted after the initial 10 patients because of the significant advantages for patients in Group 2 in comparison with those in Group 1 in regard to (1) the median number of days to absolute neutrophil count 0.5 x 10(9)/l (12 versus 21) and platelet count to 50 x 10(9)/l (13 versus 23), (2) platelet transfusions (3 versus 15.5), and (3) episodes of neutropenic sepsis (0 versus 4, respectively). One patient in Group 1 died from treatment-related complications. All patients in Group 1 required bone marrow reinfusion. No patient in Group 2 required bone marrow reinfusion, and no early mortality was observed in this group. Eight subsequent patients were treated with PBP and GM-CSF (Group 3). This group was more heavily pretreated than Groups 1 or 2 and had a slower hematologic recovery than Group 2. However, none of these patients required bone marrow reinfusion. The four patients in Group 1 that did not have early bone marrow rescue all had neutrophil counts of 0.0 on day 15. For Groups 2 and 3, the neutrophil counts on day 15 ranged from 0.3-2.1 x 10(9)/l (median, 1.9) and from 0.2-2.1 x 10(9)/l (median 0.6), respectively. CONCLUSIONS: The use of PBP plus GM-CSF accelerated hematologic recovery after this chemotherapeutic regimen compared with GM-CSF alone; there were reduced morbidity and platelet transfusion requirements. Recovery was sufficiently rapid that PBP were an acceptable alternative to autologous bone marrow transplantation in patients receiving high-dose carboplatin, etoposide, and cyclophosphamide.

Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital.

Fifty-seven adult patients with acute promyelocytic leukemia (APL) were treated between 1974 and 1984 with daunorubicin (DNR) or 4-(9-acridinylamino)methanesulfan-m-anisidide (AMSA) in combination with arabinosylcytosine (Ara-C) and 6-thioguanine (TG); they also received prophylactic heparin. Forty-one patients (72%) achieved complete remission (CR), including 11 of 12 patients who received the AMSA-containing regimen. The incidence of early fatal hemorrhage was 14%, lower than that of earlier studies or other published reports. Elevated WBC and serum lactate dehydrogenase levels at diagnosis were associated with an increased incidence of life-threatening hemorrhage and shorter remission duration. Advanced age was an unfavorable prognostic factor for male patients. Both DNR and AMSA in combination protocols are effective treatments for APL. The incidence of CR is similar to that achieved in other types of acute nonlymphoblastic leukemia (ANLL) with the same protocols, but the median duration of remission is significantly longer in APL (24 v 9 months) and the percentage of remissions longer than 60 months is also higher in APL (35% v 5%).

Human immunodeficiency virus infection in patients with leukemia.

Eighteen human immunodeficiency virus (HIV)-seropositive patients were found among 211 previously treated adult patients with a variety of leukemias who had been multiply transfused before April 1985. Patients known to be homosexual or intravenous drug users were excluded from this study. The spouse of one HIV-seropositive patient became HIV infected and subsequently developed the acquired immune deficiency syndrome. Patients with leukemia who were multiply transfused before the availability of screening of blood products for HIV antibody should be counseled regarding their individual risks of HIV infection and the risk to sexual contacts.

Hemolysis following platelet transfusions from ABO-incompatible donors.

Two hemolytic transfusion reactions related to isoagglutinins present in group O platelet concentrates are reported. The first, a severe reaction in a group A 10-kg patient, resulted from transfusion of 200 ml of plasma containing a hemolytic anti-A, titer 16, and an IgG anti-A, titer of 32,000. In the second case, a group B adult received between 50 and 70 ml of O plasma with a titer (16,000) of anti-B. This was followed by hemolysis of approximately 40 percent of the patient's red cell volume.

ABH incompatible bone marrow transplantation: removal of erythrocytes by starch sedimentation.

Nineteen patients with acute leukaemia underwent bone marrow transplantation despite major ABH incompatibility between donor and recipient. The marrow inoculum was prepared prior to infusion by admixture with hydroxyethyl starch to sediment the incompatible erythrocytes, which were then discarded. The infusion was well tolerated with two patients developing transient haemoglobinuria, seven patients developing low grade fever and 10 experiencing no reaction. Durable haematopoietic engraftment was achieved in the 18 evaluable patients and was not influenced by pre-transplant isohaemagglutinin titres. No difference in time to engraftment, incidence of GVHD or in overall survival was found, compared to ABH compatible transplants. Therefore, the presence of incompatibility did not appear to influence transplant outcome adversely. The technique described is a rapid and safe method for overcoming the ABH barrier in marrow transplantation.

A computer system designed for a hospital transfusion service.

A computer system that enhances the efficiency of a hospital transfusion service is described. It reduces the possibility of clerical errors; shortens the time elapsed between the ordering and the delivery of blood products; decreases the outdating of these units; and provides easy access to medical, demographic, and statistical information.

Red cell exchange: treatment of babesiosis in a splenectomized patient.

A splenectomized woman with a history of hepatic disorders was diagnosed as having babesiosis. The patient was unsuccessfully treated with chloroquine and with pentamidine isothionate. A parasitemia of 15 per cent was reduced permanently to less than 1 per cent after a red blood cell exchange, but a low grade parasitemia still existed 10 months after onset. On two separate occasions, the patient was found to have selective IgA deficiency, a reduction of T lymphocytes, and a reduction in function of both T and B lymphocytes. This case represents the highest and the longest duration of parasitemia ever recorded. It reports the first use of pentamidine and red blood cell exchange transfusion in human babesiosis, one of the earliest diagnosed cases of babesiosis, and the most severe clinical case to survive.

Granulocyte transfusions in infected neutropenic children with malignancies.

Thirty-six febrile neutropenic episodes were treated by granulocyte transfusions in 33 children. Septicemia and mucous membrane ulcerations were most commonly associated with the fever. Infection cleared in 81% of the episodes, eight per cent ended in death from bacterial infections, 11% from nonbacterial infections or hemorrhage. The median number of polymorphonuclear leukocytes given was 1.1 X 10(10)/m2/transfusion. Two to twenty-eight (median 8.5) transfusions were given over 3--34 days (median 10.5). The source of cells (parental or random) and the method of collection did not seem to affect the outcome. None of the 23 patients whose marrow recovered during the transfusions died of bacterial infections. Infection cleared even without marrow recovery in 62% of the patients, but then only 25% lived for more than two months after clearing of sepsis. In a subgroup of patients with nonlymphoblastic leukemia on the same chemotherapy and antibiotic treatment protocol, 8/11 (73%) survived bacteremia when white cell support was available; only 2/11 (18%) of a historical control group survived when such support was not available. Granulocyte support appears to be a valuable tool in helping neutropenic patients overcome their infections or, at the very least, helping them survive long enough for normal marrow recovery to occur.