Absence Of Platelets Research Articles

Inhibition of thromboplastin generation by hyaluronidase preparations and reversal by lyophilized platelet material and derivatives.

SummaryBovine testicular hyaluronidase preparations inhibited formation of thromboplastin in absence of platelets or equivalent materials. This effect was not due to destruction of an essential component of the coagulation mechanism. Inhibition was prevented or reversed by platelets, thromboplastin-generating components extracted from platelets and tissues and by defatted platelet material.

Defects of the clotting mechanism in blood dyscrasias and their significance in oral surgery

The defects that hinder effective blood coagulation are nearly always due to either lack of a plasma coagulation factor or a serious diminution or absence of platelets. Information concerning this is usually volunteered by the patient or readily obtained from a history, and often it is obtained from inspection of the patient. Confirmation and more detailed data can be learned from routine and easily performed laboratory tests. Any surgical treatment afforded these patients should be as conservative as possible and should be performed only to give relief obtainable in no other way. They should be premedicated in order to correct the specific abnormality as much as possible, and procedures should be performed with the greatest possible care. Adequate precautions to prevent postoperative infection are essential. Frequently, a period of postoperative bleeding is to be expected, and sufficient preparations to control this and to compensate for it should be made in advance. Finally, each case of a patient suffering from one of the foregoing diseases will present its own special problems in addition to those discussed here or in the literature. Their proper resolution is dependent upon the good clinical judgment and knowledge of the practitioner.

An Experimental Approach to the Origin of Blood Platelets

Approximately the earliest known recorded reference to the idea that blood platelets existed as a definite entity was on March 7, 1842 at the Academy of Science in Paris by Donne.?15> He stated that there existed in the blood, red and white globules and little globules, globulins. There seems to be no earlier recognition of the blood platelet as a formed element of the blood. Hayemc(15 concluded in 1882 that the platelet thrombus played an important part in the arrest of bleeding, and that a decrease or absence of platelets should result in the mechanism of hemostasis. A year later (1883) Krauss (15) reported in one form of hemorrhagic disease, Hemorrhagic purpura, when the number of platelets suddenly rose from a very low point, the hemorrhage ceased. More of Hayem's workt15 at this time drew attention to the large size of the platelets and the soft quality and poor retractibility of clots formed from the blood of these patients. He attributed these defects to the decrease or absence of platelets. In 1910, Wright(22) offered the theory that platelets arose from fragmenting megakaryocytes of the bone marrow, and this theory is held to be correct by most authorities today. The problem of the origin of platelets has been made an object of intensive study and most of the evidence so laboriously accumulated is, when critically analyzed, impressingly in favor of Wright's theory. Actual formation of platelets from megakaryocytes in the peripheral blood have supposedly been noted in various pathological conditions, particularly in the leukemias. 20) The megakaryocyte is always found present in the normal adult mammalian bone marrow. The reticule-endothelial cell gives rise to the megakaryocyte by first undergoing changes to the hemocytoblast and finally the mature cell, and it is assumed that platelet production may occur wherever mature megakaryocytes exist: bone marrow, spleen, liver, and lung. (5, 9, 16, s18, 20)

Societies and Academies

LONDON. Royal Society, February 7.—G. Udny Yule: A mathematical theory of evolution based on the conclusions of Dr. F. C. Willis, F-.R.S. The fundamental assumptions are that: (i) Within any species, in any interval of time, an “accident “may happen that brings about “specific mutation,” i.e. the throwing of a new form, regarded as a new species within the same genus; (2) within any genus, in any interval of time, an “accident “may happen that brings about “generic mutation,” i.e. the throwing of a new form so different from the parent that it will be placed in a new genus. Both chances are taken as invariable within, the group considered and constant for all time. Sections I.—III. of the paper lead up to the expression for frequency-distribution of size of genus at any given time. In Section IV. the expression is tested on data for four cases, and gives very good agreement with facts, but there are serious difficulties of interpretation. In Section V., frequency-distributions of age for genera of a given size are determined. Approximately for large genera after infinite time, the mean age varies as the logarithm of the number of species, but the dispersion is considerable. When time is limited, primordial and derived genera form distinct groups. Finally in Section VI. an attempt is made to estimate the doubling period for species in flowering plants, which is placed at probably some two or three million years, the present rate of production of specific mutations probably lying between i in 15 and I in 30 years, among all flowering plants on the whole surface of the globe.—L. B. Winter and W. Smith: Studies on carbohydrate metabolism. I. Variations in the nature of the blood sugar. Marked differences exist between the blood sugar of normal persons and those suffering from diabetes mellitus. The sugar was extracted from considerable quantities of blood and a comparison made between the observed optical rotation (P) and that calculated from the reducing power of the carbohydrate, on the basis that glucose is the only reducing substance present (C). In diabetic cases, P is usually greater than C, and is increased by mild hydrolysis with weak hydrochloric acid, whereas C is unaltered. This may be evidence for the existence of complex sugars in diabetic blood. Similar substances are present in the blood of rabbits after injection of either adrenaline or thyroid alone. Injection of thyroid and adrenaline together usually causes an increase in the total blood sugar, but no change from the normal; P is low and complex sugars are absent. After injection, of insulin into rabbits the blood sugar is dextro-rotary, but has no copper reducing power. Insulin convulsions in rabbits are relieved by adrenaline alone or by a mixture of thyroid and adrenaline.—J. W. Pickering and J. A. Hewitt: The action of “peptone “and of nucleic acids on the coagulability of the blood. Intravascular injection of Witte's “peptone “into tortoises deprived of hepatic activity inhibits coagulation of blood subsequently shed. Addition of moderate concentrations of “peptone “to blood of the tortoise in vitro causes prolonged inhibition of clotting, provided the blood has not been in contact with damaged tissues. As regards rats, partly pigmented animals are more resistant to the anticoagulant action of peptone and to its toxic effect on the heart than are animals with completely pigmented fur. Albino rats are still more resistant. The rapid intravascular injection or addition in vitro of thymus or yeast nucleic acids inhibits coagulation of blood shed from, cats and rats which have been deprived of hepatic activity. Serial intra-vascular injections of thymus nucleic acid into cats or rats deprived of hepatic activity produce hyper-coagulability followed by tolerance, culminating in immunity to the anticoagulant action of nucleic acid. Immunisation can be produced with material free from protein. Anticoagulant action of thymus nucleic acid is exhibited during the presence and absence of platelets. It is suggested that nucleic acid inhibits clotting by union with plasma components, forming a more stable complex than that existent in normal circulating blood.—E. C. Grey: The latent fermenting powers of bacteria. Pts. I., II., and III. There cannot be a host of essentially different anzymes. The mechanism by which succinic acid is split into two parts cannot differ fundamentally from the mechanism by which glucose is split into two parts to form lactic acid, or three parts to form acetic acid, or into two parts to form a mixture of succinic acid and acetic acid or alcohol. It is not conceivable that the addition of formates can change one enzyme into another, as the lactic-acid-forming enzyme into an acetic-acid-forming enzyme, unless both have a common basis.

THE SYNERESIS OF BLOOD CLOTS

(1) The syneresis of gels formed in wide‐mouthed vessels after the recalcification of oxalate and citrate plasmas is modified by (2) the speed of recalcification, (b) the temperature of the plasma (c) the amount of the surfaces exposed to forces of adhesion.(2) The presence of fat globules and of “blood‐dust” in the before mentioned plasmas does not apparently affect the development of the contraction of clots.(3) The effects of variations of the speed of recalcification and of variations of temperature may be wholly or partly masked when the recalcified gel is formed in small bore tubes.(4) Release of the gel from adhesion to the vessel walls permits syneresis.(5) The development of syneresis in recalcified oxalate and citrate plasmas in contact with flat glass plates is modified by variations in temperature and by other factors at present undetermined.(6) When coagulation is delayed by the anticoagulants named, varying types of syneresis are found. Variations of temperature and the degree of exposure to the forces of adhesion modify the contraction of the clots formed.(7) During the disappearance of platelets after the intravascular injection of “peptone” and of thymus nucleic acid the clots when formed exhibit typical syneresis.(8) Blood platelets are apparently not the primary cause of syneresis.(9) Adhesion plays an important part in the inhibition of syneresis.(10) The absence of platelets may delay the contraction of clots by modifying the viscosity and adhesiveness of blood.(11) The effect of contact on the coagulation of blood is continuous up to the formation of a contracted clot.(12) Attention is drawn to the possible importance of changes of viscosity of the blood in haemorrhagic states.(13) The anomalies apparent by a comparison of the records of various workers on the coagulation and syneresis of normal and of pathological bloods are commented on.The authors are indebted to Dr P. A. Levene for a most generous supply of pure thymus and yeast nucleic acid.

THE PATHOGENESIS OF PURPURA HEMORRHAGICA WITH ESPECIAL REFERENCE TO THE PART PLAYED BY BLOOD-PLATELETS

The hemorrhagic diathesis of chloroform and phosphorus poisoning is without doubt due to a deficiency of fibrinogen in the blood and that of a type of melena neonatorum to a retarded rate or complete failure of blood coagulation. The hemorrhages of jaundice and hemophilia can perhaps be accounted for by abnormal blood coagulation, although proof of this is not so clear as in the former diseases. The disease with which I shall deal in this paper, namely purpura hemorrhagica, has apparently an entirely different pathogenesis and, it is believed, is due wholly or partly to an almost complete absence of platelets from the blood. That the number of platelets in the blood is reduced in purpura hemorrhagica was first observed in 1887 by Denys, a histologist, and later by Hayem, the discoverer of blood-platelets. Denys 1 reported three cases in which platelets could hardly be found in fresh blood films.

THE RELATION OF BLOOD PLATELETS TO HEMORRHAGIC DISEASE

It is my purpose in this paper to report three cases and experiments which furnish additional evidence to show that the blood platelets play a part in stopping hemorrhage, and that one type of hemorrhagic disease may be attributed to an extreme reduction in the number of platelets. The cases possibly explain the relief which sometimes follows transfusion in hemorrhagic disease. It is my purpose also to describe a method for studying hemorrhage called the bleeding time, and to describe briefly a simple method for determining the coagulation time. In the cases there was marked hemorrhagic diathesis, a normal coagulation time, and almost an absence of platelets. Transfusion was performed in each case. After transfusion there was a marked increase in the number of platelets and remarkable relief of hemorrhage. When the platelet counts returned to their previous low level, hemorrhages returned. Later in the course of the disease in