David A. Sears

The morbidity of sickle cell trait: a review of the literature.

Abstract The extensive literature describing abnormalities associated with sickle cell trait has been reviewed. It is weighted with uncontrolled series and anecdotal reports, and the frequency of complications of sickle trait is, with few exceptions, undefined. Many early reports, written before hemoglobin electrophoresis was widely available, suffered from imprecise identification of the sickle hemoglobinopathies and the probable inclusion of patients with doubly heterozygous disorders or even homozygous sickle cell anemia among those with the sickle trait. In addition, extrapolation of abnormalities occurring in sickle cell anemia to the trait and undue reliance on postmortem findings of intravascular sickling as indicative of a pathogenetic role of sickle trait have flawed some reports. There is evidence that sickle cell trait does not impair survival, and controversy exists as to whether certain occupations, such as those involving flying, diving or extreme exertion, are unduly hazardous for people with AS hemoglobinopathy. There is convincing evidence that certain abnormalities do occur with increased frequency in the sickle cell trait. Among tese are hyposthenuria, renal hematuria, bacteriuria and pyelonephritis in pregnancy, and splenic infarction with high altitude hypoxia. Other real hazards may exist for the person with sickle cell trait, but these await convincing demonstration by properly controlled studies.

The anemia of chronic disease: Spectrum of associated diseases in a series of unselected hospitalized patients

PURPOSE Previous studies of the anemia of chronic disease (ACD) have generally begun with patients afflicted with one of the classical underlying diseases such as rheumatoid arthritis. The clinical spectrum of ACD has not been thoroughly examined. We hypothesized that many patients have an anemia with the characteristics of ACD but do not have one of the infectious, inflammatory, or neoplastic disorders usually associated with ACD. We therefore evaluated a series of consecutive, unselected, anemic patients admitted to a county hospital. PATIENTS AND METHODS All patients admitted to the medicine ward service of a county hospital were screened for anemia (hematocrit less than 40% in men, less than 37% in women). Additional laboratory data were collected on all anemic patients, except those with active gastrointestinal bleeding, hemolytic disease, or leukemia or multiple myeloma. The patients were divided into three groups on the basis of serum values indicating iron distribution: iron deficiency (serum ferritin less than 10 ng/mL), ACD (serum iron less than 60 micrograms/dL and serum ferritin more than 50 ng/mL), and all others (non-ACD). The hospital records of the patients in the latter two groups were reviewed and their diagnoses recorded. RESULTS Seven patients with iron deficiency were not considered further. Ninety patients with ACD were compared with 75 patients with non-ACD. The anemia in ACD patients was more severe than most authors describe. The mean hematocrit was 31%, and 20% of patients had hematocrits below 25%. The anemia was usually normocytic (mean red cell volume [MCV] 86 fL), but 21% had an MCV less than 80 fL. The level of saturation of serum iron-binding capacity was quite low in ACD (mean 15%) and was normal in non-ACD (mean 31%). Renal insufficiency was common in both groups; serum creatinine values were more than 2 mg/dL in 31% of patients with ACD and 20% of non-ACD patients. Sixty percent of patients with ACD had a principal diagnosis that fell into the infectious, inflammatory, and neoplastic categories commonly associated with ACD. Renal insufficiency was the major diagnosis in 16%, and the principal diagnosis in 24% was a disease not commonly considered to be associated with ACD. In non-ACD patients, the principal diagnosis was an infectious, inflammatory, or neoplastic disease in 55%, renal insufficiency in 9%, and another disease in 36%. CONCLUSIONS When ACD was defined by the abnormalities of iron distribution, which are its most consistent and widely accepted characteristics, the spectrum of associated diseases was much broader than the traditional categories of infectious, inflammatory, and neoplastic disorders, and the overlap with non-ACD was large. Until the etiologic and pathogenetic mechanisms of ACD are better understood, a flexible and inclusive view of this disorder seems appropriate.

Anemia of chronic disease.

ACD is probably the most common anemia among hospitalized medical patients. It is variably defined by its clinical and, particularly, its laboratory manifestations. The most consistent features are low serum iron and normal or increased serum ferritin levels, reflecting normal or increased iron stores and distinguishing ACD from iron deficiency anemia. ACD often coexists with iron deficiency and the anemia of renal insufficiency. Most patients have an underlying infectious, inflammatory, or neoplastic disease, but as many as one quarter of patients do not. Several mechanisms have been proposed, the most significant of which are a block in reutilization of hemoglobin iron for red cell production and relative deficiency of erythropoietin, but the pathogenesis and mediators involved remain uncertain. The anemia itself seldom requires treatment and is ameliorated by successful treatment of the underlying disease.

Donor cell leukemia : Report of a case occurring 11 years after allogeneic bone marrow transplantation and review of the literature

We report the case of a man with chronic myelocytic leukemia (CML) and a 46,XY,t(5;9;22) karyotype who developed acute myelocytic leukemia (AML) with a 45,X,t(8;21) karyotype 11 years after bone marrow transplantation (BMT) from his HLA‐matched sister. Fluorescent in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the new leukemia to be of donor cell origin. Donor cell leukemia (DCL) after BMT is rare. Our review of the literature found 15 cases following BMT for leukemia and 2 cases after BMT for benign hematological disorders. In fewer than half the reported cases were molecular studies available to confirm the cytogenetic evidence for DCL, and the longest previously reported interval between BMT and DCL was 6 years. Am. J. Hematol. 63:46–53, 2000.

Pica, iron deficiency, and the medical history

We describe two new forms of pica associated with iron deficiency and a new variant of a third. Previous reports on pica are tabulated. The value of a sympathetic, nonjudgmental approach to eliciting the medical history is emphasized.

Intravascular hemolysis due to intracardiac prosthetic devices: Diurnal variations related to activity

Abstract Studies are described on two adult patients in whom intravascular hemolysis developed following open heart surgery in which intracardiac prosthetic materials were implanted. In one patient an ostium primum interatrial septal defect was closed using a Teflon patch. In the other a Starr-Edwards caged ball-valve prosthesis was used to replace the aortic valve. In the first patient there was a striking pattern of diurnal hemoglobinuria, and subsequent investigations revealed a consistent relationship between activity (and, therefore, presumably cardiac output) and the rate of hemolysis as judged by urinary hemoglobin output and plasma heme pigment levels. These findings support the concept that hemolysis in such patients occurs as a result of intracardiac mechanical damage to red cells. The plasma heme pigments were identified as free hemoglobin and methemalbumin which were present in fairly consistent proportions, the latter accounting for the majority of the plasma pigment. Iron studies demonstrated a significant urinary iron loss even with minimal hemoglobinuria. It was suggested that plasma transaminase increases in these patients might be a result of intravascular release of the enzyme from hemolyzed red cells. The implications of the findings for diagnosis, treatment and prognosis of this syndrome of mechanical intravascular hemolysis have been explained.

Bone Marrow Histiocytic Hyperplasia and Hemophagocytosis with Pancytopenia in Typhoid Fever

Typhoid fever was associated with pancytopenia in five patients. Bone marrow examinations revealed histiocytic hyperplasia with marked phagocytosis of platelets, leukocytes, and red blood cells in these individuals. This phagocytosis may contribute to the pancytopenia that occurs in some patients with typhoid fever. The striking degree of the histiocytic hemophagocytosis is reminiscent of the malignant disease, histiocytic medullary reticulosis. The importance of careful exclusion of infectious etiologies in illnesses involving marrow histiocytic proliferation is emphasized.

Carboxyhemoglobin Levels in Patients with Sickle-Cell Anemia: Relationship to Hemolytic and Vasoocclusive Severity

Background: When carbon monoxide binds to hemoglobin, it increases the affinity of hemoglobin for oxygen and shifts the oxygen dissociation curve to the left. The resulting decrease in sickling tendency could have clinical benefit, and carbon monoxide has been suggested as a treatment for sickle‐cell disease. Furthermore, in sickle‐cell disease, as in other hemolytic diseases, endogenous carbon monoxide production is increased because of increased heme catabolism. Methods: In the present study, we measured carboxyhemoglobin levels in sickle‐cell patients and compared them with estimates of the hemolytic and the vaso‐occlusive severity of the disease. Results: Significant correlation was found between carboxyhemoglobin (HbCO) levels and hematocrit, reticulocyte count, unconjugated bilirubin level, and percentage of irreversibly sickled cells. However, there was no significant correlation between carboxyhemoglobin levels and measures of the vaso‐occlusive severity of the disease. Conclusions: The correlations between HbCO levels and measures of hemolytic severity are best explained by the known relationship between hemoglobin catabolism and CO production. The lack of correlation with vaso‐occlusive severity may be due to the complex changes involved and the difficulty of quantifying vaso‐occlusive severity.

Pure red cell aplasia associated with hepatitis C infection.

We report the case of a 34-year-old woman with recurrent pure red cell aplasia and evidence of hepatitis B and C infection. Review of the English literature identified 19 prior cases in which pure red cell aplasia was associated with hepatitis. This case is the first in which serologic evidence of hepatitis C infection was documented. This patient also had porphyria cutanea tarda and marked hepatic siderosis but no active hepatitis or cirrhosis. Treatment with cyclophosphamide and prednisone produced complete remission of the pure red cell aplasia. Erythroid colony formation (colony-forming unit-erythroid and erythroid burst-forming unit) was reduced in cultures of bone marrow obtained during relapse but was normal in remission marrow. However, addition of the patient serum, whether collected during relapse or remission, inhibited erythroid colony formation by her bone marrow. These observations, and the known extrahepatic immunologic manifestations of hepatitis C infection, suggest that the pure red cell aplasia occurred because of autoimmune mechanism provoked by the infection.

Delayed hemolytic transfusion reaction in sickle cell disease

ABSTRACT: This article reports the details of delayed hemolytic transfusion reactions in four patients with sickle cell disease. These cases demonstrate the characteristics of the reactions, the significant risks involved, and the principles useful in diagnosis and treatment. Patients with sickle cell disease are at particular risk for delayed hemolytic transfusion reactions because they may be transfused at intervals over many years; they frequently form alloantibodies because of antigenic differences from the donor population; and they may receive emergency care in different hospitals where transfusion records are not available. In addition, exchange transfusions, which are often used for patients with sickle cell disease and which were given in three of these cases, raise the risks through increased exposure to foreign erythrocyte antigens and through an increased volume of erythrocytes susceptible to hemolysis. It was concluded that the hazards of these transfusion reactions justify preventive measures, such as extended erythrocyte phenotyping of patients with sickle cell disease and extended phenotypic matching of transfused cells.