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W Haire

Publications and source records attributed to W Haire.

6 recordsLinked to original sources

Factors predicting morbidity following hematopoietic stem cell transplantation.

Circulating anticoagulants protein C (PC) and antithrombin III (AT) are markers of, and possibly involved in the pathogenesis of, significant organ dysfunction, in patients undergoing autologous peripheral blood stem cell (PSBC) or autologous bone marrow (BM) transplantation. The effect of the stem cell source, the use of hematopoietic growth factors (GFs), and the specific preparative regimen on the incidence of organ system dysfunction or on post-transplant levels of circulating anticoagulants has not been well studied. We analyzed 205 patients in an attempt to correlate organ dysfunction and AT and PC deficiencies with these transplant-specific factors (78 BMT with GM-CSF after transplant, 95 PBSCT without GM-CSF after transplant, and 32 PBSCT with GM-CSF after transplant). Patients transplanted with PBSC had a lower incidence of pulmonary dysfunction (20 vs 40%, P = 0.006) and liver dysfunction (4 vs 13%, P = 0.05) than patients receiving BM. The use of GF after transplant did not influence the development of subsequent organ dysfunction. In multivariate analysis, the stem cell source was again predictive of pulmonary dysfunction. In contrast, although patients transplanted with PBSC also had a lower incidence of PC deficiency (50 vs 81%, P < 0.01) and AT deficiency (20 vs 54%, P < 0.01) as compared with patients receiving BM, use of GM-CSF after transplant was a more significant risk factor for the development of anticoagulant deficiency (PBSC with GF vs PBSC without GF: PC deficiency 50 vs 78%, P = 0.007; AT deficiency 20 vs 47%, P = 0.005). In the multivariate analysis GM-CSF use was the only significant risk factor for development of anticoagulant deficiency. Since the clinical significance of anticoagulant deficiency has been well shown, further studies examining these effects of hematopoietic GFs appear warranted.

Antithrombin III Deficiency

Prolonged deficiency of protein C following hematopoietic stem cell transplantation.

Deficiencies in circulating anticoagulant protein C (PC) occur in patients undergoing hematopoietic stem cell transplantation. These deficiencies may predispose to thrombotic and other complications, and may contribute to the morbidity of transplantation. In most patients, PC reaches a nadir 14 days after the preparative regimen and then begins to increase toward normal. However, low PC has been seen months after transplantation. Neither the frequency of, nor risk factors for, this prolonged deficiency are known. We examined 71 adults undergoing stem cell transplantation and found low PC antigen and activity in 21% and 20% of patients, respectively. Low PC at day 100 correlated strongly with low PC pre-chemotherapy (PC antigen, r = 0.69, P < 0.001; PC activity, r = 0.59, P < 0.001). The incidence of deficiency of PC at day 100 was lower in patients undergoing peripheral stem cell transplantation compared with patients undergoing autologous BMT (12.5% vs 35%; P = 0.05), although several significant confounding variables exist. We conclude that deficiencies in protein C persist at least 100 days after stem cell transplantation in nearly one quarter of patients undergoing this procedure. Therefore, patients undergoing stem cell transplantation may be at prolonged risk of thrombotic and other complications. Further studies to determine the risk of prolonged deficiency based on stem cell source need to be performed.

Adult

High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma.

To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgkin's lymphoma. Patients received either weekly (standard dose group) or daily (high dose group) vitamin K supplements with their total parenteral nutrition. By day 14 there had been a significant drop in protein C activity (mean of 95% of normal to 52%), protein C antigen (mean of 105% of normal to 70%), and antithrombin 3 activity (111% of normal to 83%), and an increase in fibrinogen (471-621 mg/dl) and tissue plasminogen activator (6.9-13.8 ng/ml). No changes were seen in free or total protein S, plasminogen activator inhibitor, prothrombin time or partial thromboplastin time. The decreases in protein C and antithrombin 3 persisted through day 28 after transplantation. The drop in protein C correlated strongly with decrease in serum albumin, suggesting impaired synthesis of these proteins by the liver. No differences were seen in any of these parameters between the standard and high dose groups. Deficiencies in anticoagulant proteins antithrombin 3 and protein C and a rise in fibrinogen without a concomitant improvement in fibrinolytic variables create a potentially hypercoagulable state which may contribute to the thrombotic complications of autologous BMT.

Adult

Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients.

PURPOSE: The purpose of our work was to evaluate pulmonary complications in autologous bone marrow transplant recipients. PATIENTS AND METHODS: A total of 141 consecutive autologous bone marrow transplant recipients were evaluated. In 29 patients, a clinical syndrome characterized by progressive dyspnea, hypoxia, cough, diffuse consolidation on chest roentgenography, and characteristic bronchoalveolar lavage findings developed over one to seven days. RESULTS: In 29 patients, bronchoalveolar lavage performed by sequential instillation and aspiration of 20-ml aliquots of normal saline resulted in recovered lavage fluid that became progressively bloodier with each recovered aliquot. Autopsy and bronchoalveolar lavage in these patients revealed no pathogens that accounted for the clinical findings. Since the later aliquots sample predominantly alveolar material, this syndrome was termed diffuse alveolar hemorrhage (DAH). DAH was associated with a high inpatient mortality rate (23 of 29 died versus 14 of 112 without DAH, p less than 0.001) and was associated with age over 40 years, solid malignancies, high fevers, severe mucositis, white blood cell recovery, and renal insufficiency (p less than 0.05, compared with patients without DAH). However, DAH was not associated with prolonged prothrombin or partial thromboplastin times or decreased platelet counts compared with patients without DAH. CONCLUSION: DAH is a frequent cause of respiratory compromise and a major cause of mortality in autologous bone marrow transplant recipients.

Adult

Coma and thyrotoxicosis.

A patient with Graves' disease was in coma with evidence of corticospinal tract disease. Treatment with standard pharmacological measures and plasmapheresis resulted in the reduction of total thyroxine from 28.8 micrograms/dl to 10.0 micrograms/dl and of triiodothyronine from 332 ng/dl to 150 ng/dl. These laboratory findings were associated with clinical stabilization, improvement of mental status, and resolution of the findings of corticospinal tract disease. These data support previous contentions relating reversible corticospinal tract disease to thyrotoxicosis.

Adult