Aortic atherosclerosis and stroke.

METHODS: Studies using transesophageal echocardiography (TEE) suggest aortic atherosclerosis may be a risk factor for stroke, particularly stroke of undetermined mechanism, but controls in prior studies were not balanced for vascular risk factors. We used TEE to evaluate aortic atherosclerosis in 60 patients with stroke compared with a high-risk control population of 46 subjects. We also examined the possible association of plasma viscosity and fibrinogen levels to aortic atherosclerosis. RESULTS: The mean maximal plaque thickness (MMPT) was similar for the control (2.8 +/- 3.6 mm) and the stroke group (3.3 +/- 3.5 mm), but varied with stroke mechanism. The MMPT was similar in stroke of undetermined and atherosclerotic mechanism [3.5 +/- 4 mm (n = 25) and 4.2 +/- 4.3 mm (n = 16), respectively], significantly greater than in stroke of other mechanisms (1.7 +/- 1.2 mm, P < .05, n = 19). Patients with stroke of undetermined mechanism were four times more likely (95% confidence interval [CI] 1.2-12) to have plaques >/=5 mm compared with controls. Ulcerated plaque was associated with plaque thickness (P < .001) and plasma viscosity (P < .001). CONCLUSIONS: Aortic atherosclerosis is associated with stroke of undetermined cause suggesting atherosclerosis is a cause of stroke of undetermined etiology. Plaque ulceration was associated with the thickness of aortic plaque and plasma viscosity.

Chronic relapsing thrombotic thrombocytopenic purpura.

A 58-year-old man had anemia and thrombocytopenia immediately after a myocardial infarction; recovery occurred spontaneously, but relapses followed intercurrent infection and abdominal surgery. The terminal relapse was precipitated by gastric ulcer with hemorrhagic gastritis; this episode was characterized by fluctuating neurologic symptoms including coma. Autopsy studies confirmed the diagnosis of thrombotic thrombocytopenic purpura. This case shows that thrombotic thrombocytopenic purpura may occur de novo in adults as a relapsing syndrome with exacerbations precipitated by diverse events characterized by inflammation or tissue necrosis.

The effect of donor age on the flow properties of blood. Part I: Plasma and whole blood viscosity in adult males.

The relationship between blood viscosity and age was studied using heparinized blood samples obtained from 50 normal male blood donors between the ages of 20 and 65 years. There was a slight but significant decline in packed cell volume (hematocrit) with age. Plasma viscosity showed no significant variation with donor age, but the viscosity of blood samples standardized to a packed cell volume of 45 ml/dl showed an increase as the age of the donor rose. The age-related trend to a higher viscosity was present at shear rates below 46 s-1, but not at higher shear rates. This shows that with age there is a rising trend in the red cell contribution to blood viscosity, which is not dependent on the packed red cell volume; this component increases across a wide age range in early and middle adult life, and is not a characteristic appearing exclusively in later age periods. The tendency for the viscosity trend to be greater at lower shear rates indicates increased shear thinning in blood obtained from older subjects, the cause of which may be either diminished red cell deformability in these subjects, or an increased tendency to form aggregates at low shear rates.

Abrogation of calcium exclusion by erythrocytes under hypotonic stress.

Normal human erythrocytes in isotonic suspension maintain a high gradient of calcium ion concentration across the membrane, with the cytosol [Ca2+] several orders of magnitude below plasma concentration. Despite the high degree of exclusion maintained against the entry of Ca2+, the osmotic resistance of red cells in hypotonic saline is significantly augmented by the presence in the medium of Ca2+ in concentrations greater than 0.07 mmol/l. Resistive particle spectroscopy showed this to occur without alteration of the mean critical haemolytic volume; furthermore, in the presence of Ca2+ there was a reduction in cell volume at prolytic osmolalities when compared with cells in calcium-free sodium chloride solutions. This is shown to be due to augmentation of the prolytic loss of K+ in the presence of Ca2+ through calcium-sensitive channels, and indicates that the pathway for passive K+ efflux uncovered in the prolytic state is indistinguishable from that of normal passive K+ diffusion. It is also demonstrated that the prolytic red cell membrane is permeable to Ca2+ and admits the divalent cation to the inner aspect of the plasma membrane. These changes are comparable to those of cells prior to haemolysis in vivo, as in the irreversibly sickled cell, and are therefore not specific to the latter condition.

Age as a factor affecting erythrocyte osmotic fragility in males.

Osmotic fragility and erythrocyte dimensions were measured in 40 normal males between the ages of 18 and 78 years. The principal independent variables correlating with osmotic fragility were mean cell haemoglobin concentration and the age of the donor. The age-related effect was shown to increase both the mean fragility of the cells and the variability of the fragilities of the cells within the individual blood sample. The physical basis for the change is an increase in the degree of isometric sphering of the erythrocytes at isotonicity. The change in shape does not appear sufficient to affect capillary perfusion significantly in normal subjects, but suggests that cell shape will increase the vulnerability of the elderly to abnormalities of the microvasculature.

The modification of human erythrocyte membrane structure by membrane stabilizers: an electron spin resonance study.

Membrane structure in intact human erythrocytes was analyzed by electron-spin-resonance (ESR) spectroscopy. The spin probes 5-doxyl stearate and 5-doxyl stearate methyl ester revealed thermally-induced structural transitions in the membrane at 37 degree C and 15 degree C. The addition of propranolol, diazepam, chlorpromazine, or Pluronic F68 all caused a decrease in the temperature of the upper transition, but did not markedly alter the temperature of the lower transition. In addition, diazepam caused a significant decrease in the ordering or packing of the membrane-lipid acyl chains. It is proposed here that the protection from hypotonic hemolysis that has been reported in the presence of these drugs is mediated by a structural rearrangement in the erythrocyte membrane involving a change in protein-lipid interactions.

Pseudoleukemia: when "leukemia" is not leukemia.

Several case reports6-8 in the literature have pointed out that a clinical and morphologic picture resembling that of acute leukemia may be secondary to infection or use of toxic drugs or alcohol. In these cases, the leukemic picture spontaneously returns to normal when the precipitating factor is no longer present. This condition has been termed pseudoleukemia. Unless the history of a precipitating factor is clear, the patient may be wrongly treated for leukemia. In the case reported here, initial findings suggested acute promyelocytic leukemia and chemotherapy was planned, but further investigation indicated that the condition was essentially reactive and related to a presumed viral infection. Even though pseudoleukemia is sometimes described as a leukemoid reaction, we believe that the term "pseudoleukemia" should be reserved for more specific differentiation.

Therapy with factor IX concentrate resulting in DIC and thromboembolic phenomena.

The development of subclinical DIC in a patient with factor IX hemophilia receiving concentrate replacement therapy during surgery is discussed with respect to pertinent laboratory features. Subsequent thromboembolic phenomena are presented in the context of current literature. Of significance is the failure of heparin given with the factor IX concentrate to prevent DIC. The value of adequate laboratory monitoring during therapy is stressed.

The role of the spleen and splenectomy in autoimmune hemolytic disease.

The relationship of the spleen to the red cell in AHDW is determined by the characteristics of the surface protein coating of the red cell, rather than by a pathologic change in the reactivity of the spleen. The behavior of the spleen is essentially a passive response to red cells with abnormal properties. The critical properties are incompletely defined, but probably include cell shape, and perhaps more importantly, the intrinsic properties of the cell membrane. The effects produced by the spleen are mediated partly by the filtration mechanism of the splenic sinus walls, and partly by the more specific effects of cell-to-cell adhesion between the pulp macrophages and the red cells. The outcome is more complex than former concepts of red cell destruction encompassed: delay in cell passage produces cell pooling in the unfavorable environment of the splenic pulp, and there is microfragmentation, cell sphering, and partial phagocytosis, in addition to cell destruction with erythrophagocytosis in situ. Prediction of the degree of dependence of hemolysis on the spleen prior to splenectomy remains an area of uncertainty. Commonly, the decision for splenectomy is determined circumstantially, but current concepts would anticipate that the most relevant data would relate to the dimensions of splenic pooling, and the quantity and class of immunoglobulin present on the cells.