Mario Stefanini

Platelets: VII. Shortened “Platelet Survival Time” and Development of Platelet Agglutinins Following Multiple Platelet Transfusions.

Summary 1. The rate of platelet disappearance or platelet survival time was followed at regular intervals in 4 patients with hypoplastic or aplastic anemia receiving repeated transfusions of platelet-rich polycythemic blood or of isolated platelets as supportive therapy. As transfusions were repeated, in 3 of these patients, a) survival time of platelets became progressively shorter, b) administration of platelets was less and less effective in the control of the bleeding manifestations. In one patient a platelet agglutinin was detected in the serum. 2. Search for platelet agglutinins was conducted in the serum of 11 patients who had Received multiple blood transfusions over a period of months. A low titer platelet agglutinin was detected in one case. This patient developed mild thrombocytopenia and exhibited shortened platelet survival time. 3. These findings suggest that “refractoriness” to the therapeutic effect of the administration of platelets may develop in patients receiving multiple platelet or blood transfusions. This may be due to the development of antiplatelet substances in the serum, at least in individual cases.

Thromboplastic Activity of Leukemic White Cells.

Summary Some types of white cells collected from leukemic patients (granulocytes, monocytes) but not others (lymphocytes, eosinophiles) release thromboplastic material. The extracted material is able to correct the coagulation defect of hemophilic plasma in vitro.

Studies on platelets. IV. A thrombocytopenic factor in normal human blood, plasma, or serum.

Summary 1. Temporary, but significant thrombocytopenia was noted in 32 out of 36 individuals receiving compatible blood, plasma or serum from non-thrombocytopenic donors. No spontaneous bleeding manifestations, alterations of the various hemostatic mechanisms, changes in number or activity of the bone marrow megakaryocytes, alterations of function or morphology of the remaining platelets, agglutinating or lysing activity of the recipients serum against normal platelets were noted. Heparinization of the recipient did not affect the thrombocytopenic effect of the transfusion of compatible plasma. 2. The thrombocytopenic effect was apparently due to a component of plasma, stable at 56°C, no absorbed by Seitz filters nor by ion-exchange resins, but absorbed on Ca3(PO4)2 gel from which it could be eluted with sodium citrate solution. Work is in progress to establish the nature, the mechanism of action of this agent, and its relation to products of platelet destruction.

Fibrinolysis. I. Fibrinolytic activity of extracts from non-pathogenic fungi.

Summary A study of properties of extracts from cultures of 160 non-pathogenic fungi has shown that 4 cultures produce non protein materials able to lyse plasma clots and fibrin, both human and bovine source; at least one shows some specificity against human plasma clots.

Gaisböck's Syndrome: Its Hematologic, Biochemical and Hormonal Parameters

The syndrome of plethora without splenomegaly, leukocytosis, or throm bocytosis was described by Gaisböck in 1905. It was reevaluated in 25 patients through the study of numerous hematologic and biochemical parameters. Sta tistically significant findings included mild obesity; elevation of blood pressure (especially diastolic); decrease in plasma volume with relative increase in red cell count, hemoglobin, hematocrit, viscosity of blood, elevation of plasma proteins, serum cholesterol, triglycerides, uric acid, and plasma renin; and increased excretion of urinary sodium. The reduction in plasma volume seemed related to the elevation of the diastolic blood pressure, and favorable through temporary therapeutic results were produced by some antihypertensive agents. The elevation of serum cholesterol, triglycerides, and uric acid, the increased blood viscosity, and the elevated plasma renin were reminescent of the biochem ical changes observed in some instances of hypertension and atherosclerotic disease. They may explain why patients with the Gaisböcks syndrome belong to the high risk group of hypertensive individuals who often develop cardiovascu lar complications. While its long-term effects remain to be evaluated, treatment with nondiuretic antihypertensive drugs may help reduce the incidence of these complications.

Hemorrhagic Diathesis with Ascorbic Acid Deficiency During Administration of Anterior Pituitary Corticotropic Hormone (ACTH).

Summary 1. Two patients developed hemorrhagic manifestations presumably due to ascorbic acid deficiency while receiving high doses of anterior corticotrophic hormone (ACTH). The criteria for such a diagnosis are discussed. 2. Ascorbic acid deficiency is probably not a common occurrence in the course of ACTH therapy, but should be considered if hemorrhagic manifestations appear during prolonged administration of the hormone, when other factors of hemostasis are above critical levels.

Characteristic Electrophoretic Patterns in Hemophilia and Idiopathic Thrombocytopenia.

Summary Characteristic electrophoretic patterns have been observed in all 5 cases of hemophilia and in all 8 cases of idiopathic thrombocytopenic purpura. These patterns show the following characteristics: (a) appearance of an unusual peak in the group of the α-globulins (αx), and (b) disappearance of the usual α2- and α3-globulin peaks. The same anomaly has been observed in some cases of secondary thrombocytopenia, “anaphylactoid” type of vascular purpura, and hemolytic anemia with evidence of platelet dysfunction.

Electrophoretic Plasma Protein Patterns in Families with Hemophilia.

Summary 1. An electrophoretic anomaly, called αx-globulin, has been found in the plasma of 14 hemophiliacs, i.e., in all of the active bleeders studied. 2. The same anomaly also has been observed in 8 members of hemophilic families who are not active bleeders (over 50% of this category), and who are not afflicted with any of the other diseases in which this anomaly has been found. 3. The electrophoretic anomaly is seen in female as well as in male subjects unlike the bleeding manifestation of hemophilia, found only in males. 4. There is a definite relationship between the prothrombin utilization and the appearance of the αx-globulin anomaly in the plasma of members of hemophilic families.

Vasopressor effect of synthetic 5-hydroxytryptamine creatinine sulfate in man.

Summary 1. Intravenous injection of 0.3 γ/min. 5-hydroxytryptamine creatinine sulfate (5-HT) caused transitory elevation of local venous pressure; higher doses induced more marked elevation of local venous pressure and, when administered in short period of time, of arterial pressure. Elevation of systemic venous pressure was not obtained even with extremely high doses of 5-HT. 2. Intraarterial administration of 5-HT induced sustained elevation of pressure in the homolateral veins (30 minutes or longer). 3. Elevation of arterial pressure and generalized flushing followed injection into a patient with septal venous-arterial shunt of a dose of 5-HT unable to cause such effect in normal subjects. 4. It is postulated that injected 5-HT is quickly removed from the circulation, perhaps by platelets or by other cellular elements retained in capillary beds and released slowly at a later time.

Fibrinolysis III. Nutritional and Environmental Requirements for Optimum Production of Fibrinolysin from Aspergillus (Aspergillin O)

Summary A method is described for obtaining higher yields of fibrinolytic material (Aspergillin O) from cultures of Aspergillus oryzae (B-1273) by addition of trace minerals (zinc, iron and manganese) to the liquid medium, incubated at room temperature and in darkness.