ALTERATIONS OF THE HEMOSTASIA 
IN PATIENT WITH DIABETIC FOOT 


_______________________________________________________________________________ SANDOVAL DIANA; SUA LUZ DARY ¨ November, 1999 


Summary
The alterations in the hemostasia constitute a decisive factor in the complications of the diabetes mellitus. The changes in the factors of the coagulation, especially levels of PTT, fibrinogen and antithrombin III, they contribute in great measure to the development of the complications in patient with diabetic foot, in which an activity hipercoagulation, product of those metabolic alterations is observed. To check the existence of factors altered in the patient's hemostasia, an investigation was developed with a group of 20 people that suffered diabetic foot and they were carried out hemostasia tests, to be able to determine if these patients had or not altered this tests. In pro of carrying out a treatment preservative with anticoagulants that avoid the trombos formation and the faulty irrigation of the tissues, causing of the member's terrible amputaciónes and in many cases of the whole inferior extremity. 

Introduction
The diabetes mellitus is an illness that can take to serious dysfunctions, if it is not diagnosed and treated, in an appropriate way and appropriately. (1)

Graph 1. Ulcer of degree 3 (ostemielitis)
In foot neuroisquemico

The well controlled diabetes doesn't present secondary dysfunctions; however, in many cases same complications of the illness are presented like the retinopatía, neuropatía, nefropatía, vascular illness, diabetic foot, etc. (6,12,19,20,25,27)

The diabetic foot is one of the complications that worries most of the diabetics, due to its affection degree in the person. 
The diabetic foot is one of the consequences of the diabetes mellitus, manifested physically in a late and latent way, from symptoms like dry skin and insensibility of inferior members, until serious dysfunctions like ulcerations. (5,15) 
These ulcerations are the main cause foot loss, due to infections of the affected area, causing the gangrene formation and finishing finally in the terrible amputation of the member y/o of the whole inferior extremity. (25,27) 
The complications of the diabetes are closely related with the alterations in the hemostasia, being observed a significant change in the levels of Fibrinogen, antithrombin III, and in smaller proportion a lingering PTT. 
The diabetes type that the patient presents with diabetic foot, in general is the Diabetes Mellitus type 2. 
The affections of the foot, they have been divided in different degrees, in this study the classification of the University of Texas was used. 
(Isquare 1). (2,16,17)


Isquare 1. Classification of the diabetic foot
Degree 
0 I II III
A Pre or post ulceration. Lesion completely epitelializada . Injure clean and clear . Superficial lesion through the epidermis and dermis. Injure clean and clear. Lesion that penetrates tendon or capsule. Injure clean and clear. Lesion that penetrates bone or articulation. Injure clean and clear. 
STATE B Pre or post ulceration. Lesion completely epitelializada Injure infected non isquémicas. Superficial lesion through the epidermis and dermis. Injure infected non isquémicas. Lesion that penetrates tendon or capsule. Injure infected non isquémicas. Lesion that penetrates bone or articulation. Injure infected non isquémicas. 
C Pre or post ulceration. Lesion completely epitelializada. Not injure infected isquémicas. Superficial lesion through the epidermis and dermis. Not injure infected isquémicas. . Lesion that penetrates tendon or capsule. Not injure infected isquémicas. Lesion that penetrates bone or articulation Not injure infected isquémicas. 
D Pre or post ulceration. Lesion completely epitelializada. Injure infected and isquémicas. lesion through the epidermis and dermis. Injure infected and isquémicas. Lesion that penetrates tendon or capsule. Injure infected and isquémicas. Lesion that penetrates bone or articulation. Injure infected and isquémicas

Fuente: Validation of a Diabetic Wound Classification System.Armistrong David





The hemostasia constitutes the process by means of 
which a blood vessel that has suffered a wound and a hemorrhage, stops the flow of blood to avoid their loss . (21,24) 
For such a reason, it can be evidenced clearly that if a person presents alterations in the hemostasia, the repercussions on the tissues and affected organs will be abnormal. 
The obstruction of the blood vesseles, added to the faulty sanguine irrigation and the bad nutrition of the tissue, they bear in the diabetic patient the formation of ulcerations and other dysfunctions that besides rebounding in the mental health and the person's physics, they wrap the family environment. 
To determine the effect of the alterations in the hemostasia a group of patient with diabetic foot was studied, finding results that indicate the abnormality in the function of coagulation. 
The fibrinogen like factor of the coagulation intervenes in the fibrina formation, in the normal process of repair of the blood vessel, to seal the wound and to avoid the loss of blood; and as another function it is to act as protein of sharp phase in the inflammation. When existing an abnormal process for the alteration of the fibrinogen level, the blood spreads to form trombos that cork the blood vessel and capillary. (31) 
The antithrombin III (A.T III) as inhibitor of the clotting, it is the responsible for the degradation of the trombina, the breakup of the trombo and the reestablishment of the normal blood flow. (31) 



Materials and Methods 

For the development of the investigation was taken a sample among the diabetic population of Occidente Kennedy's Hospital, corresponding to a number of 20 people that presented diabetic foot, with different affection degree; in their entirety all of them were subjected to some tests of coagulation, evaluated and analyzed according to the following approaches. 
To determine the effect of the alterations in the hemostasia, these patients were subjected to the tests of Time of Protrombina (PT), time of partial tromboplastina (PTT), plaquetas recount (PQ), fibrinogen (Fbr) and antithrombin III. (AT III). 
The samples taking was carried out according to biosecurity rules, with the respective cautions to avoid loss of information or alterations in the sample that took to erroneous results. 
Besides the diabetic foot they were also kept in mind other factors that can contribute to the illness, like the arterial hypertension, the age, the sex, the cholesterol and other enclosed factors. (4,10,11,13)


Results 

The analyzed data show that the laboratory tests present an alterations of the hemostasia, like they are, fibrinogen, antithrombin III (A.T III) and partial thromboplastin time (PTT) in smaller proportion. The other tests didn't go so important results at the moment to conclude that these patients with diabetic foot, present an abnormal coagulation function. 

In this study I take into account a general analysis of the results for each one of the tests. 
You also determines the proportion of patients detected with alterations hemostáticas for each one of the tests of laboratory deacuerdo with the degrees of diabetic foot. Keeping in mind the distribution of frequency and the comparison by means of graphics of boxes for each degree of diabetic foot with reference to the daily control in the tests of PT, PTT and to the reference values in the tests of recount of plaquetas fibrinogen and ATIII. The carried out tests showed that for a significant number of diabetic patients, the fibrinogen levels were high, those of antithrombin III (A.T III) first floor and those of PTT some lingering ones. 
(Chart 1). 


Comments 

The diabetic foot in their primary manifestation, degree zero, is present in all the diabetic people; of there the importance in the prevention of the development of a severe complication that bears to an ulceration and then to the amputation. 

The changes that exist in the mechanisms hemostáticos are a factor of risk in the person with diabetes mellitus, since these alterations rebound directly in the sanguine flow, causing irrigation problems toward the tissues. 

The tests carried out the 20 patients with diabetic foot have some important results, presented next. 85% of these patients presents high levels of fibrinógen, decrease of antitrombin III and 60% of the patients they had a lingering PTT. In the other studied tests, PT and plaquetas recount they were found that they didn't have a significant percentage of values altered with regard to the daily controls and to the reference values. 

The fibrinogen levels can be increased in the patients with diabetic foot, The fibrinogen levels can be increased in the patients with diabetic foot, due to a desencadenamiento of the inflammation where interactúan among other, the interleuquinas like for example: the interleuquina 6, the one which, it reinforces the hepatocitos in the production of the proteins of sharp phase as they are: the protein C reactivates, the fibrinogen among others. (22) 
On the other hand, these patients in their majority didn't present some vascular illness demonstrated by means of the observation of the clinical history and the Doppler. Some studies show that the fibrinógeno is increased in patient with diabetes mellitus (DMK), with vascular problems and that they have certain factors of risk like they are: the age, the cigarette, the cholesterol, the hypertension among others. This increase of the fibrinogen happens mostly in patient with diabetes mellitus type 2 that with type 1 (4, 10). 
In the studies of you Talk 116 patients they took with diabetes mellitus; 80 patients were managed with (DMK) type 2 and 36 (DMK) type 1, giving 11 as a result (DMK) type 2 and 3 patients (DMK) tipo1 with fibrinogen elevations. 
In our study 16 patients they were (DMK) type 2 and 4 (DMK) type 1, presenting high levels of fibrinogen in 14 patients (DMK) type 2 and 3 (DMK) tipo1, having encuenta some factors of risk, already mentioned previously that they can influence in the test. 
Relating the 2 studies, it was observed that in our study, a bigger proportion was given in the high levels of fibrinogen with regard to the one of you Talk in the two diabetes types. 
The antithrombin III is diminished in patient with diabetes mellitus, in primary form to a decrease of the heparansulfato concentration in the membrane glomerular, causing that doesn't notice to the antithrombin III and therefore that it is eliminated by the urine. (8) 

In this study the ATIII is presented with an identical behavior of decrease in the four degrees of diabetic foot; however, the decrease is more notorious in the degrees I and II. 

The increase of the fibrinogen and the decrease of the antithrombin III, they are an added difficulty to develop thrombosis in the places of more risk, such as coronary, cerebral arteries or of the inferior members. 

In our study the tests of PT and PTT show very little clinical meaning in the diabetic foot, because these factors evaluate the extrinsic and intrinsic road, which are stabilized when is formed the trombo. 
In patien The continuation of the PTT in this study, it can be due for a physiologic process where the factors begin to consume for some normal process among quotation marks that he/she makes the diabetic patient as it is it the formation of a trombo (logically until certain range, it can be normal this prolongamiento but data or figures are not had until the moment). on the other hand, they would enter to play a paper the inhibitors like for example: the antithrombin III, the one which, we find in this diminished case and it intervenes in the inhibition of the trombina and other factors like Xa, XIa,IXa among others. 

The cause of the changes of the factors of the clotting is not clear. However the patients that have microangiopatias and aterosclerosis associated to the diabetes present abnormal changes in the hemostasia like for example I eat an increase of the aggregation plaquetaria for example, due to the glicolisación of the proteins of the membrane of the plaqueta (13). 

Presently study the plaquetas recount was among the normal values, because these patients didn't present any cause, either for decrease in the plaquetas production or for an increase in the destruction of the same ones.
We cannot conclude yes the results of the tests carried out the patients, correspond to a physiologic or pathological process, since we didn't make complementary tests to ratify the why of these alterations. Therefore identifying the cause of the alteration was not inside the objectives of us but only to determine if there was or not. 


Conclusions and Recommendations

The picked up information of the laboratory tests allowed to check that alterations exist in the hemostasia, in patient with diabetic foot; that which 85% (17/20) of the patients with diabetic foot presented values of high fibrinogen (>400mg/dl). 
85% (17/20) of the patients with diabetic foot presented values d and AT III first floor (<82%). 
These altered values of fibrinogen and antithrombin III can be related with a bigger thrombosis risk in inferior members. 
The decrease of the AT III and the increase of the fibrinogen, are presented in the four degrees of diabetic foot, especially in the degrees I and II. 

In accordance with the results in this study, they think about the following points: 
To study if there is presence of alterations in other factors of the clotting (C, S protein etc) that they can participate in the severity of the diabetic foot. 
A pursuit study is recommended the patients from this study to those who were found high levels of fibrinogen and decrease of antithrombin III, to evaluate if they make thrombosis and if a treatment preservative with anticoagulants, diminishes the evolution to advanced states of diabetic foot and to look for the way to normalize the fibrinogen levels and Antithrombin III. 
A study multicéntrico is recommended, with a bigger population, in order to being able to the results obtained in this study to generalize and to standardize the appropriate treatment. 






Chart 1. Distribution of frecuency of the tests
(PT, PTT, plaquetas Recount , Fibrinogen and Antithrombin III)
in a group of 20 diabetic patients of Occidente Kennedy's Hospital
(April 1999)

DEGREE OF FOOT DIABETIC ABSOLUTE FREQUENCY RELATIVE FREQUENCY IN % % OFPT ALTERATION % OFPTT ALTERATION % OF PLAQUETAS RECOUNT ALTERATION % OF FIBRINOGENALTERATION % OF ATIII ALTERATION 
O 7 35 0 20 0 25 25
I 4 20 0 10 0 20 20
II 4 20 0 15 0 20 20
III 5 25 0 15 0 20 20
TOTAL 20 INDIVIDUALS 100% 0% 60% 0% 85% 85%



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