Decreased Platelet Adhesion Research Articles

Platelet function in essential thrombocythaemia

Platelet aggregation in response to ADP, adrenalin and collagen, platelet factor 3 availability and Rlatelet adhesiveness to glass (Payling Wright method) were studied in 14 patients with essential thrombocythaemia (mean platelet count 1.2 × 10 6 μl). Abnormalities were found in all patients. Platelet aggregation in response to adrenalin was absent in 3 patients but the most striking abnormality was an absent or very weak first phase response and a marked delay in secondary response (response time—mean 257 s) in 8 patients. The secondary response was impaired in 2 and a normal response was obtained in 1 patient. Platelet aggregation with collagen was normal in 6 but delayed response time (mean 186 s cf. control 43 s) was elicited in 8 patients. Aggregation with ADP (0.5 μg/ml) was normal in 10 with impairment of the secondary response in the remaining 4 patients. Platelet adhesiveness to glass was reduced in 10 and normal in 4 patients. No defect in platelet factor 3 availability was detected. The commonest pattern of platelet function abnormality in essential thrombocythaemia appears to be a delayed abnormal or absent aggregation response to adrenalin, decreased platelet adhesiveness to glass and delayed aggregation response time with collagen.

Abnormalities of platelet aggregation in the vaso-occlusive crisis of sickle-cell anemia

An impairment in the rate and per cent of first phase platelet aggregation with ADP was present in 10 patients with sickle-cell anemia during vaso-occlusive crises, when compared to their own base-line values and those of 20 normal control subjects. ADP released from erythrocytes or platelets could have been the mediator of this platelet “refractory state” since a concomitant decrease in platelet adhesiveness during the vaso-occlusive crises was also demonstrable. The effect of the platelet on the production or maintenance of the vaso-occlusive crisis of sickle-cell anemia requires further elucidation.

Polyphloretinphosphate, an antithrombogenic substance which inhibits platelet adhesion

Polyphloretinphosphate (PPP), a polyester of phloretin and phosphoric acid, was investigated with regard to its effect on platelet adhesion. The compound was administrated intravenously to Defibrase R-defibrinogenated dogs and to dogs with normal plasma fibrinogen. The accumulation of 51Cr-labelled platelets was measured on the surface of specially designed plastic arteriovenous shunts. In defibrinogenated dogs, PPP reduced the uptake of platelets on the foreign surface to less than five per cent of the control level. In dogs with normal plasma fibrinogen, the shunts remained patent after PPP as long as the platelet accumulation on the surface was low. PPP exerts a weak antithrombin activity, which was not, however, responsible for the beneficial effect on platelet adhesion. It is concluded that PPP contains a factor which primarily decreases platelet adhesion on a plastic surface.

Decreased adhesion of platelets to subendothelium in von Willebrand's disease.

Abstract The adhesion of platelets in flowing blood to the subendothelial surface of rabbit aorta was studied by a quantitative, in vitro method. Platelet adhension was significantly decreased in 5 patients with von Willebrand's disease. Impaired adhesion of platelets to some component of the blood vessel wall may account for the prolonged bleeding time in these patients.

Surgery in von Willebrand's disease.

Von Willebrand's disease differs from classic hemophilia by its usually milder manifestations, prolonged bleeding time, predominance of mucous membrane bleeding, and autosomal inheritance. A review of the Henry Ford Hospital experience from 1959 to 1969 revealed 19 well-documented cases and 22 probable cases. The major diagnostic criteria were (1) significant history of abnormal bleeding; (2) reduced factor VIII activity; and (3) increased bleeding time. Supplementary criteria included family history of the disease, abnormal platelet morphological findings, decreased platelet adhesiveness, and positive plasma infusion tests. These 41 patients underwent a total of 171 surgical procedures. Without specific therapy, 75 procedures were associated with normal bleeding but in 55 it was excessive. On preoperative treatment with adrenocorticosteroids and fresh frozen plasma, in 40 procedures bleeding was normal and in 3 excessive.

Alteration of platelet adhesion to glass in vascular disorders and certain other diseases.

The adhesion of platelets to glass has been quantitated in control subjects and in patients with vascular disease, diabetes mellitus, uremia, disorders of the prostate gland, or congenital deficiency of certain blood coagulation factors. Platelet adhesion was quantitated by means of a simple in vitro test which permits differentiation of adhesion from aggregation. Platelet adhesion was elevated above control values in patients with vascular diseases who were not taking anticoagulants. Decreased platelet adhesion occurred in patients with uremia and in four of five patients with disorders of the prostate gland. Marked variation in platelet adhesion values was found in diabetic patients and in patients with vascular diseases who were taking anticoagulants. Patients deficient in coagulation factors V, VIII, IX, X, or XII had normal platelet adhesion values.

Functional Studies of Young Versus Old Platelets in a Patient With Chronic Thrombocytopenia

Abstract Results of a comparative study of the functional capacity of young versus old platelets are presented. A girl with thrombopoietin deficiency, who predictably produced platelets in response to plasma transfusion, was used as platelet donor. Her platelets obtained 4 days after infusion were used as young test cells. Platelets obtained at 18 or 21 days after infusion were used as old cells. Young platelets were found to be associated with normal bleeding times, normal clot retraction, normal or increased platelet adhesiveness, normal aggregation to ADP and collagen, and normal platelet factor 3 availability. Old platelets were found to be associated with long bleeding times, decreased platelet adhesiveness in vivo and in vitro, and deficient platelet factor 3 availability. The clot retraction and aggregation to ADP and collagen of old platelets, however, was normal. No differences between young and old platelets were observed by electron microscopy.

On coagulation and fibrinolysis in conservatively treated chronic uraemia.

Abstract. Factors of the coagulation and fibrinolytic systems have been studied in 50 conservatively treated patients with chronic uraemia of varying origin and serum creatinine levels of 2.1–27.5 mg/100 ml. The patients were grouped according to serum creatinine level, aetiology of renal failure and actual treatment. The investigation showed that decreased platelet adhesiveness, prolonged Ivy bleeding time and bleeding tendency, increased content of certain coagulation factors (factor VIII, P & P, fibrinogen), decreased fibrinolytic activity and increased content of inhibitors of plasminogen activation were common. The platelet adhesiveness decreased, the bleeding time and the bleeding tendency increased with increasing serum creatinine. Factor VIII, P & P and fibrinogen tended first to rise and then to fall, while the fibrinolytic activity and the content of inhibitors of plasminogen activation did not vary with renal function. No certain correlation was found between the changes observed and the aetiology of uraemia or actual treatment.

Disseminated Intravascular Coagulation and Acute Renal Failure

SummaryStarting from a hypothesis according to which disseminated intravascular coagulation might be an intermediary mechanism in the production of acute renal failure, investigations were made in 94 cases of anuria of different etiology, in order to detect signs of a consumption coagulopathy. After an average lapse of time of 48 h since the onset of anuria, the most frequently encountered hemostatic defect was a decreased platelet adhesiveness. In vitro experiments and clinical observations suggest that in the early stage of acute renal failure caused by a septic abortion, deficient platelet adhesiveness is due, mainly to platelet damage caused by intravascular coagulation or by bacterial toxins and not by the retention of metabolites. Euglobulin lysis time was prolonged, but a significant decrease of the plasminogen level indicates that an activation of fibrinolysis might have occured in the evolution of the process.

MANAGEMENT OF PATIENTS WITH HOMOCYSTINURIA REQUIRING SURGERY UNDER GENERAL ANAESTHESIA: A Case Report

SUMMARY An 8-year-old boy with homocystinuria required a prolonged dental operation under general anaesthesia. The successful management, without subsequent thromboembolism, is described. The patient showed a partial response to treatment with pyridoxine over a two-year period. The response was marked by a reduction in the plasma and urinary homocystine levels and by decreased platelet adhesiveness. It is suggested that a similar regime of pre-operative and operative management should be considered in all affected patients undergoing surgery, since there was no increase in platelet adhesiveness by the third postoperative day, as would normally have occurred.

Comparison of the Effects of Various Blood Plasma Expanders on Platelet Adhesiveness

SummaryIn 30 non-anesthetized rabbits, platelet adhesiveness of arterial blood was determined before and 2, 6, and 24 h after 10 min intravenous infusions of either 20 ml isotonic saline solution (5 control rabbits), or 2.4 g each of dextran 40,000 (4 rabbits), dextran 70,000 (4 rabbits), polyvinylpyrrolidone (P. V. P.) 40,000 (8 rabbits), hydroxyethyl starch (H. E. S.) 60,000 (4 rabbits), or H. E. S. 450,000 (5 rabbits) in saline solution.Platelet adhesiveness did not change significantly after infusions of saline, dextran 40,000, or H. E. S. 450,000. In contrast, dextran 70,000 and H. E. S. 60,000 promptly produced about one-third decrease in platelet adhesiveness which returned toward control levels 24 h after the infusions. Finally, P.V.P. also promptly diminished percent platelet adhesiveness by about one-third of control values and this effect persisted 24 h after infusion. Changes in platelet adhesiveness did not correlate with alterations in hematocrit or platelet count.On a weight basis, P. V. P. elicits the most persistent decrease in platelet adhesiveness.

Beneficial Effect Associated with Use of Watery and Alcoholic Extract of Garlic as a Supplement in Hyperlipidemic Guinea Pigs

Background: Garlic is naturally occurring sulphur containing dietary agent belong to Allium family. Members of this family i.e. Garlic, Onions are found to have beneficial effect on atherosclerosis and ischemic heart diseases in both experimental animals and in human beings. Objective: To compare the potency of garlic as antihyperlipidemic and antiplatelet and antithrombotic between its watery and alcoholic extract for their effects. Methods: 25 guinea pigs were fed cholesterol (0.5g/kg body weight) for an initial period of 4 weeks. Cholesterol was then discontinued and the animals were divided into 3 groups. Group-I (n=7) was fed with stock diet and was taken as control. Group-II (n=9) was given 1ml of watery extract and Group-III (n=9) was fed with 1ml of alcoholic extract of garlic with normal diet daily for 4 weeks. The garlic content of both the extract was 2 gm/ml by wt/vol. Fasting blood samples were collected at the end 4 weeks and finally at the end of the study i.e.8 weeks for estimation of serum cholesterol, serum triglyceride, LDC-C, HDL-C, VLDL-C, atherogenic index and platelet adhesiveness index. Bleeding time and clotting time were also detected in all the 3 groups. Results: In the present study, the watery and alcoholic extract of garlic shows significant hypolipidemic activity as they reduced significantly serum cholesterol, serum triglyceride, LDC-C, VLDL-C and atheriogenic index in hyperlipidemic guinea pigs (p<0.01) compared to control. The significant rise in HDL-C was observed in group II but not in group III animals. On comparison between two extracts, watery extract of garlic was more potent hypolipidemic agent, compared to alcoholic extract. Both extract significantly reduces platelet adhesiveness and bleeding time. But between two extract the watery extract was found more potent anti-thrombotic agent as it showed significant decrease in platelet adhesiveness (P<0.01). BT was significantly increased in group II compared to group I and III. Conclusion: It can be concluded that watery extract of Allium Sativum is more potent hypolipidemic and antiplatelet, and anti-thrombotic agent. Key Words: Allium Sativum; Hyperlipidemia; platelet adhesiveness index; watery and alcoholic extracts. DOI: http://dx.doi.org/10.3329/jbsp.v6i1.8079 J Bangladesh Soc Physiol. 2011 June; 6(1): 22-26

Platelet adhesiveness in von Willebrand's disease.

A glass bead test for platelet adhesiveness is described in which heparinized blood can be used. Anticoagulation allows the blood to be handled more conveniently and, furthermore, the flow rate can be exactly controlled. By means of this test, decreased platelet adhesiveness has been demonstrated in von Willebrand’s disease, and the difference between von Willebrand’s disease and normal is much greater than that demonstrated by the Salzman test. Evidence is presented to suggest that the abnormality is due to the absence of a plasmatic factor.

Platelet Adhesiveness and Euglobulin Lysis Time in Dogs Given Repeated Infusion of Sodium Palmitate

SummaryThe effect of infusions with sodium palmitate 3.5 m Mol/1 on platelet adhesiveness and euglobulin lysis time was studied in 16 dogs. A decrease of platelet adhesiveness was noted 15 min after infusion. Decreased platelet adhesiveness persisted 3 and 24 hrs later, although platelet counts that were diminished 15 min after the infusion, returned to the initial level. Fibrinogen levels were not found to decrease during infusions of fatty acids. A progressive increase of plasma fibrinogen was even noted in animals that survived more than 7 days after the first infusion. Following a transient acceleration of euglobulin lysis time, a delayed fibrinolysis was noted, probably as a result of the exhaustion of blood activator.Fibrin depositions were emphasized in histological sections. In some animals aspects of obliterative thromboangiitis were noted. However bilateral cortical necrosis was found in only 1 dog.It seems that correlations between increased lipid mobilization and changes of coagulability and fibrinolysis in atherosclerosis are much more complex.

Investigation of patients with mild thrombasthenia--a haemorrhagic disorder with prolonged bleeding time probably due to a primary platelet defect.

Abstract Fifteen families with a haemorrhagic disorder are reported. The patients had a bleeding tendency characterized by easy bruisability, nose bleeding, menorrhagia and bleeding after tooth extractions, accidents or surgery. Laboratory investigation showed prolonged Ivy bleeding time and usually decreased platelet adhesiveness, as measured by Hellem's whole blood method, Salzman's method and occasionally Hellem's plasma‐ADP method. Factor VIII and other coagulation factors were normal. The prothrombin consumption test was mostly normal and there was no pathologic fibrinolysis. The inheritance was probably dominant, but the penetrance weak. The disease was probably caused by a primary platelet defect, especially since a similar syndrome was found among relatives of a family with severe thrombasthenia of Glanzmann's type. We call the condition mild thrombasthenia.

Effect of Unsaturated Fatty Acid Supplements upon Mortality and Clotting Parameters in Rats Fed Thrombogenic Diets

The adhesiveness property of blood platelets has been implicated in the development of thrombosis; therefore, platelet adhesiveness and other clotting parameters were studied in rats receiving the Thomas-Hartroft diet as such and as modified by supplementation with unsaturated fatty acids. Rats receiving the Thomas-Hartroft thrombogenic diet for 4 months were found to have decreased platelet adhesiveness, thromboplastin generation and platelet count. Since platelet adhesiveness is reported to increase in coronary-prone individuals, the thrombogenic diet studied does not appear to produce changes characteristic of the thrombotic tendency in man. The mortality of rats receiving the Thomas-Hartroft diet was reduced by supplementation of the diet with concentrates of linolenic, linoleic or oleic acid. However, the decreased platelet adhesiveness could be prevented by linolenic or linoleic acid, but not by oleic acid; thrombocytopenia was prevented by supplementation of the diet with linolenic acid, but linoleic and oleic acids afforded only partial protection; the decrease in thromboplastin generation could be significantly reversed only by linoleic acid. Thus, although mortality could be reduced by all 3 unsaturated fatty acids, changes in the clotting parameters studied were not necessarily affected by these treatments; and therefore, it is unlikely that these clotting parameters are involved in either the increased mortality induced by these diets or its reversal.

VON WILLEBRAND'S DISEASE ASSOCIATED WITH INTERMITTENT THROMBOCYTOPENIA

Four cases of von Willebrand's disease Summary accompanied by intermittent thrombocytopenia in three generations of a family are described. Possible explanations for the coincidence of these two conditions are that the thrombocytopenia is inherited in close linkage with von Willebrand's disease or that it is part of the disease. It is tentatively suggested that decreased platelet adhesiveness caused by lack of a plasma factor leads to increased loss of platelets during each bleeding episode. These reports stress the importance

IN-VIVO AND IN-VITRO EFFECTS OF POLYVINYLPYRROLIDONE ON PLATELET ADHESIVENESS IN HUMAN BLOOD

Intravenous infusion of 500 ml. 6% polyvinylpyrrolidone (P.V.P. (Mw 40,000) in isotonic saline solution over a 2-hour period significantly diminished platelet adhesiveness in eight subjects from 27% before infusion to as low as 10% at the end of the infusion. 5 hours after the end of the infusion, platelet adhesiveness was still significantly reduced (16%). The addition of P.V.P. to citrated blood in vitro significantly decreased platelet adhesiveness. Both in vivo and in vitro, the platelet-count was not significantly altered by P.V.P. The in-vivo change in platelet adhesiveness is similar to that reported by others with dextran-a plasma expander that differs chemically from P.V.P.

Effect of Dextran infusion on the Adenosine Diphosphate Induced Adhesiveness and the Spreading Capacity of Human Blood Platelets

SummaryThe adenosine diphosphate induced platelet adhesiveness to glass and the platelet spreading capacity on a siliconized glass surface have been studied in 8 hypovolemic subjects after infusion of 500 ml 6% solution of dextran 70 (Macrodex®) or 500 ml normal saline. Infusion of dextran caused a significant decrease in platelet adhesiveness compared with the controls while no effect was noted on the spreading capacity.It is proposed that the observed effect on platelet adhesiveness is due to dextran induced changes in the activity of plasma factors involved in the mechanisms leading to platelet adhesiveness.

The Platelet Function of the Thrombopathy on the Åland Islands

SummaryIn the summer of 1962 we checked a total of 20 bleeders from Åland in order to elucidate the pathogenesis of the haemorrhagic diathesis on the Åland Islands/Finland (“hereditary pseudohaemophilia” – “constitutional thrombopathy” – “v. Willebrand’s disease”). They partly belong to the same families described in 1933 by v. Willebrand and R. Jürgens. We came to the following results :1. On the determination of the volumetric retraction under consideration of the heamatocrit value 17 of 19 patients presented a hyporetractility of the coagulum.2. The thrombelastogram showed in 14 out of 18 patients a completely normal blood coagulation and only in 4 cases a very slight prolongation of the clotting time (increase of r and k).3. The clot retraction disturbance could not be normalized by adding tissue thromboplastin to the venous blood of the 4 patients with mild hypocoagu-laemia mentioned under no. 2. The hyporetractility of the coagulum can therefore not be due to the hypocoagulaemia or a lack of the intrinsic system of thromboplastin generation.4. In 18 out of 19 patients there was a partially extremely decreased platelet adhesiveness on glass surfaces.5. In 17 out of 19 patients a disorder of the platelet agglomeration in citrated plasma released by the effect of glass surfaces was established.6. 14 out of 16 patients showed a pathologic rotation thrombelastogram.7. It is possible, but not yet proved that all these phenomenons are caused by the decreased platelet adhesiveness on glass. In any case, however, the decreased platelet adhesiveness on glass speaks in favor of a disturbed platelet function which could possibly play a part in the development of the haemostatic defect in this disease. Whether we are dealing with an endothrombocytic defect, or whether the decreased adhesiveness on glass presents a secondary disorder of the platelet function due to the lack of an antibleeding factor, is another question which could not yet be definitely settled. Investigations concerning this question are continued.