Hemophilia. I. The Abnormal Coagulation of the Blood and Its Relation to the Blood Platelets

Patek, Arthur J.; Stetson, Richard P.

doi:10.1172/jci100806

Cited by 110 publications

(43 citation statements)

References 15 publications

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“…For this reason a normal " prothrombin time " would not necessarily mean that the addition of more prothrombin could not force the coagulation mechanism toward clot formation, and hence decrease the coagulation time of the blood. It becomes necessary therefore to know whether the clot promoting activity of plasma described in earlier investigations published from this laboratory (1,2) can exist in the absence of prothrombin.…”

Section: Discussionmentioning

confidence: 99%

The Coagulation Defect in Hemophilia: The Clot Promoting Activity in Hemophilia of Berkefelded Normal Human Plasma Free From Fibrinogen and Prothrombin 1

Lozner¹,

Kark²,

Taylor³

1939

J. Clin. Invest.

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Previous investigations in this laboratory have shown that normal human plasma rendered free from cellular elements, by Berkefeld filtration, is capable of reducing the coagulation time of the blood of patients with hemophilia both in vitro and in vivo (1). It has also been demonstrated that this coagulation activity of the plasma was associated with the globulin fraction of the plasma proteins (2, 3). The published data do not however identify the active material as a protein, nor do they differentiate it from fibrinogen and prothrombin, constituents of the globulin fraction which also play a role in blood coagulation. Indeed " globulin substance " as prepared by previous methods was known to contain both prothrombin and fibrinogen (2). The present communication concerns a study of the clot promoting activity of nornal human plasma, after the removal of prothrombin and fibrinogen. PREPARATION OF MATERIALSSeveral authors (4, 5, 6) have described methods for the removal of prothrombin from blood plasma. These methods consist essentially of adsorption of this substance on the hydroxides of aluminum, calcium, or magnesium. Chew (7) has suggested recently that following filtration through Seitz filters (calcium magnesium aluminum iron silicate) a prothrombin free filtrate of plasma can be obtained.By the use of the Quick et al. technique (8) it is possible to obtain a measure of the amount of prothrombin contained in preparations made from plasma.2 Table I 1The expenses of this investigation were defrayed in part by a gift to Harvard University from Smith, Kline, and French Laboratories, Philadelphia; and by a grant given in honor of Francis Weld Peabody by the Ella Sachs Plotz Foundation.2All plasmas studied were derived from normal human 0.25 per cent citrated blood centrifuged 30 minutes at 2000 r.p.m., filtered through 2 thicknesses of Number 2 Whatman paper and then through a Berkefeld V filter.shows the " prothrombin times " of certain of these preparations. It will be observed that while preparations with commercial aluminum hydroxide were quite inefficient the use of aluminum hydroxide C-gamma (9) gave preparations relatively free from prothrombin. The amount of prothrombin remaining depended upon the number of times the adsorption was repeated. More striking results were obtained however by passing Berkefeld filtrates of citrated normal human plasma 5 times through Seitz filters using fresh pads for each filtration. In addition to being prothrombin free these preparations had the advantage of being sterile. On the basis of these observations the Seitz filtration method was used routinely for the removal of prothrombin from plasma. Each batch of plasma treated in this manner was tested for prothrombin by the Quick technique and none was found. The presence of fibrinogen in the Seitz filtrate was demonstrated by the formation of a clot upon the addition of fresh serum as a source of thrombin. In one typical experiment one-tenth ml. of such serum clotted one-tenth ml. of the Seitz filtrate in 29 seconds.Plasma...

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Section: Discussionmentioning

confidence: 99%

The Coagulation Defect in Hemophilia: The Clot Promoting Activity in Hemophilia of Berkefelded Normal Human Plasma Free From Fibrinogen and Prothrombin 1

Lozner¹,

Kark²,

Taylor³

1939

J. Clin. Invest.

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“…In hemophilia, the blood is known to contain normal amounts of prothrombin, accelerator globulin, fibrinogen, and platelets. The coagulation defect in this disease can be overcome by a substance present in normal plasma (11). Hemophilic blood is known to clot normally in the presence of various thromboplastic agents.…”

Section: Discussionmentioning

confidence: 99%

“…Elucidation of the r6le of this plasma factor has largely depended upon the observation of apparent alterations in its activity in pathologic states. Thus, the coagulation defect in hemophilia seems best explained by deficient activity of a plasma thromboplastic factor (11).…”

mentioning

confidence: 99%

Studies on the Initiation of Blood Coagulation. Ii. An Anticoagulant Inhibiting the Activation of a Plasma Thromboplastic Factor 1

Conley¹,

Ratnoff²,

Ellicott³

et al. 1950

J. Clin. Invest.

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“…In general the standard procedure followed was the same as that used in previous studies (1,3) When test substances were to be assayed they were pipetted into the test tubes prior to the addition of the blood. Further mixing was not found necessary.…”

Section: Methodsmentioning

confidence: 99%

The Coagulation Defect in Hemophilia. The Effect in Hemophilia of Intramuscular Administration. Of a Globulin Substance Derived From Normal Human Plasma 1

Pohle¹,

Taylor²

1937

J. Clin. Invest.

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The recent investigations of Patek and Stetson (1) 2 indicate that the defect in coagulation of blood in hemophilia resides in the plasma rather than in the platelets. Patek and Taylor (2, 3) 2 isolated a substance from citrated normal cellularfree plasma, by isoelectric precipitation, with which was associated the clot-promoting factor of normal plasma. This substance was effective, both in vitro and after intravenous injection, in reducing the coagulation time of hemophilic blood. By the same method, a similar substance in approximately the same quantity was obtained from citrated hemophilic plasma, but its clotaccelerating power on hemophilic blood was much less marked. In the absence of definite knowledge concerning the nature of the effective material it was called "globulin substance " which is the nomenclature that will be retained in this communication. The material was thermolabile, insoluble in water, partially soluble in physiological saline solution, and non-diffusible. It was precipitated in optimal amounts between pH 5.9 and 6.4. The material passed readily through a Berkefeld filter without loss of potency and was almost completely inactivated by small excesses of alkali (3). Bendien and Creveld (4) have isolated a substance, by dilution and acidification, from normal serum which they injected intramuscularly and intravenously and report favorable results.Patek and Taylor's (3) studies imply that in some respects hemophilia is a deficiency disease in which certain factors present in normal cellular-free plasma are either reduced or modified. The present communication reports a study of the effects of intramuscular administration of 1 The expenses of this research were defrayed in part by a gift to Harvard University from Smith, Kline and French Laboratories of Philadelphia.2 Review of literature here.globulin substance on the blood coagulation time of hemophilic subjects, and on the content of a clot-promoting factor in the blood following such administration. METHODSCoagulation time. In general the standard procedure followed was the same as that used in previous studies (1,3) When test substances were to be assayed they were pipetted into the test tubes prior to the addition of the blood. Further mixing was not found necessary.Immediately after the addition of whole blood, duplicate tubes were placed in a water bath at 37.50 C.

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Hemophilia. I. The Abnormal Coagulation of the Blood and Its Relation to the Blood Platelets

Cited by 110 publications

References 15 publications

The Coagulation Defect in Hemophilia: The Clot Promoting Activity in Hemophilia of Berkefelded Normal Human Plasma Free From Fibrinogen and Prothrombin 1

The Coagulation Defect in Hemophilia: The Clot Promoting Activity in Hemophilia of Berkefelded Normal Human Plasma Free From Fibrinogen and Prothrombin 1

Studies on the Initiation of Blood Coagulation. Ii. An Anticoagulant Inhibiting the Activation of a Plasma Thromboplastic Factor 1

The Coagulation Defect in Hemophilia. The Effect in Hemophilia of Intramuscular Administration. Of a Globulin Substance Derived From Normal Human Plasma 1

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