Search

Chronic transfusion of packed red blood cells, in addition to other ongoing treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other supportive measures, was given to a splenectomized hemoglobin E/β-thalassemia woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma thrombin-antithrombin III complex (TAT) levels and right-sided cardiac catheterization were used to monitor changes after treatment. Reduction of plasma TAT levels from 7.5 to 3.8 μg/L (normal, 3 ± 2.4 μg/L), pulmonary vascular resistance (PVR) from 553.8 to 238.6 dyne.sec.cm-5 (normal, 67 ± 30 dyne.sec.cm-5), and mean pulmonary arterial pressure from 51 to 32 mm Hg (normal, 9 to 19 mm Hg) occurred in tandem. Normalization of blood hypercoagulability as reflected in plasma TAT level by chronic blood transfusion was the likely basis for improvement of increased PVR, being secondary to thrombotic pulmonary arteriopathy and subsequently PHT. (Blood. 2004;103: 2844-2846)

Introduction Pulmonary hypertension (PHT) associated with thalassemia hemoglobinopathy is now an accepted clinical entity. Due to a high prevalence of thalassemia hemoglobinpathy worldwide, it is the most common entity of PHT. Despite the commonness, its pathogenesis is not yet completely understood. Although asplenia is a known risk factor, PHT does not develop in all splenectomized patients. The present study was therefore done to search for other associated features. Patients and Methods Sixty-one clinically stable splenectomized hemoglobin E/β-thalassemia disease (E/β-Thal) adult outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks, were prospectively studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Transthoracic echocardiogram was used to evaluate cardiac function and to estimate pulmonary artery systolic pressure (PASP). PHT was defined as an estimated PASP ≥36 mmHg. Clinical features and laboratory data were dichotomized according to the presence (PHT+) or absence (PHT-) of PHT, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value

Abstract 2156 Introduction: Clinically significant pulmonary arterial hypertension (PAH) has been reported in splenectomized hemoglobin E/β-Thalassemia patients. Like primary PAH, the underlying basis is hypercoagulability related thrombotic pulmonary arteriopathy, which results in an increased pulmonary vascular resistance. In the non-splenectomized counterparts with no clear evidence of hypercoagulability only mild PAH is found. To evaluate role of splenomegaly and the accompanying increased blood volume in the pathogenesis of PAH in this group of patients, we studied the relationship between spleen volume and PA pressure. Patients and Methods: Nineteen clinically stable hemoglobin E/β-Thalassemia outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were first analyzed in this ongoing study. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (ID 07–53-01). PA pressure (PAP) was estimated by a single echocardiologist (T.Y.) using Philips iE33 echocardiographic system with a S5 probe (Philips Medical Systems, Andover, MA). Spleen volume was determined by CT scan with non-contrast, 320-slice, 3 mm axial cut (Aquilion one, Toshiba, Japan). Statistical analysis of clinical and laboratory data was done by SPSS version 18 (SPSS Inc, Chicago, Ill), considering a P value Conclusions: Non-splenectomized patients with hemoglobin E/β-Thalassemia have elevated PAP in proportion to spleen size, likely secondary to elevated blood volume. This situation is distinct from the pathologic PAH that results from increased pulmonary vascular resistance in splenectomized patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 2014 Poster Board I-1036 Introduction: Clinical manifestations of blood hypercoagulability, such as pulmonary arterial hypertension (PAH) and ischemic stroke, are well known in patients with thalassemia. We herein present evidence that the hypercoagulable state in β-Thalassemia disease patients is to a significant extent the result of prior splenectomy. Patients and Methods: One hundred and ten clinically stable hemoglobin E/β-Thalassemia outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Echocardiogram was used to estimate systolic PA pressure (SPAP). Clinical features and laboratory data were stratified according to the presence or absence of the spleen, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value Results: Of the 110 patients, 61 were asplenic and females comprised 51% in both groups. Selected statistically significant results are shown in the table . Results Asplenic (61 Patients) Non-splenectomized (49 Patients) P value Age at 1st transfusion (median) 4.7 years 17 years Total transfusions (median) 35 units PRBC 13 units PRBC 0.005 Systolic pulmonary artery pressure 37.1 +/- 14.6 mm Hg 28.8 +/- 7.6 mm Hg Cardiomegaly 50.9% 27.3% 0.013 Extramedullary hematopoiesis 50.9% 27.3% 0.013 RBC count 3.19 +/- 0.57 × 106/μL 3.87 +/- 1.09 × 106/μL Corrected reticulocyte count (median) 5.2% 1.4% Nucleated RBC (median) 581/100 WBCs 5/100 WBCs Corrected WBC count 9.72 +/- 4.2 × 103/μL 6.71 +/- 2.3 × 103/μL Platelet count 726 +/- 215 × 103/μL 243 +/- 115 × 103/μL Serum ferritin (median) 1,892 ng/mL 1,050 ng/mL 0.001 ALT (median) 65.5 u/L 44.5 u/L 0.004 AST (median) 64 u/L 36 u/L 0.001 Free hemoglobin (median) 4.2 mg/dL 2.5 mg/dL 0.001 C-reactive protein (high sens) (median) 2.7 mg/L 1.2 mg/L 0.012 Thrombin-antithrombin complexes 3.5 μg/L 1.1 μg/L Soluble P-selectin 113.4 +/- 31.2 ng/mL 56.4 +/- 32.1 ng/mL Soluble E-selectin 43.3 +/- 21.5 ng/mL 29.5 +/- 18.4 ng/mL 0.003 Conclusions: In comparison with non-splenectomized hemoglobin E/β-Thalassemia patients, asplenic ones have higher SPAP, more severe hemolysis, more liver impairment and chronic iron overload, significant chronic low grade inflammation, and evidence of coagulation activation. Splenectomy should be more judiciously applied than heretofore, and if performed, measures to blunt or prevent a subsequent hypercoagulable and inflammatory state, which could lead to PAH should be initiated. Disclosures: No relevant conflicts of interest to declare.

2015 Poster Board I-1037 Introduction: Pulmonary arterial hypertension (PAH) associated with thalassemia (Thal) hemoglobinopathy is now an accepted clinical entity. Most of the reports are in sickle cell disease and splenectomized β-Thal patients. Once manifested, it connotes poor prognosis. We herein present its prevalence and predictors in hemoglobin E/β-Thal (E/β-Thal) patients. Patients and Methods: One hundred and ten clinically stable E/β-Thal outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Echocardiogram was used to estimate systolic PA pressure (SPAP). PAH was defined as an estimated SPAP ≥36 mmHg. Clinical features and laboratory data were stratified according to the presence or absence of PAH, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value

Human factor VIII was purified from cryoprecipitate and subjected to enzymatic degradation with plasmin, trypsin, chymotrypsin, and thrombin. The reactions were monitored by sodium dodecyl sulfate (SDS)-Polyacrylamide gel electrophoresis and by measurement of four biologic properties, namely, procoagulant activity, ristocetin cofactor activity, precipitation by heterologous antibody, and neutralization of a human factor VIII inhibitor. The electrophoretic patterns of reduced digests showed a reproducible sequence of degradation of the 215,000 molecular weight subunit by plasmin, trypsin, and chymotrypsin, each with well-defined intermediate and enzyme-resistant chain remnants. There were striking similarities in the sizes of several intermediate chain remnants produced by these three enzymes, suggesting the presence of regions on the factor VIII molecule that are especially susceptible to enzymatic degradation, but each enzyme also produced distinctive proteolytic derivatives. The most obvious differences included (1) a single-chained 40,000 molecular weight remnant cleaved by plasmin and trypsin which was either absent or degraded in chymotryptic digests, (2) large intermediate chain remnants of 176,000 and 157,000 molecular weight which were produced only by trypsin, and (3) differences in size and content of nonreduced fragments in the final digests. Thrombin caused no detectable change in electrophoretic patterns. The immunoprecipitation reaction was sensitive to minor degrees of proteolytic cleavage, showing a marked increase in rocket size even when the SDS-treated subunit chains showed virtually no change in electrophoretic mobility. Procoagulant and inhibitor neutralizing activities were rapidly destroyed by trypsin and plasmin, but this destruction did not correlate with specific changes in electrophoretic patterns. Both thrombin and chymotrypsin caused an increase in procoagulant activity prior to destruction of activity; changes in this property were therefore unrelated to changes in the protein visualized by gel electrophoresis. Ristocetin cofactor activity was considerably more resistant to plasmin than to trypsin or chymotrypsin, and roughly paralleled the persistence of highly aggregated forms in the digests.