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PubMed1979

Blood coagulation and hereditary nephritis.

Nineteen patients with hereditary nephritis - members of six families - were studied for haemostasis on 11 occasions by the use of four capillary tests, 14 different blood coagulation tests and two different platelet function tests. Systemic capillaropathy was demonstrable in 8 out of 15 cases of the non-uraemic, and in all the 5 cases of the uraemic group. No completely normal blood coagulation was found in any of the cases and the coagulation disorders were never of exclusively haemorrhagic pattern. On the evidence of the complex studies, hypercoagulability as well as hyper-hypocoagulability were found in the uraemic and non-uraemic groups alike. Reduction in plasma fibrinolytic activity, elevation of the fibrinogen level and a shift of the thrombelastogram in the direction of thrombosis were demonstrable in the majority of the cases.

Adolescent↗
PubMed1977

Platelet consumption by arterial prostheses: the effects of endothelialization and pharmacologic inhibition of platelet function.

The thrombogenic mechanism of arterial grafts has been studied by determining the relative utilization of platelets, fibrinogen and plasminogen by human arterial prostheses, and by direct examination of arterial grafts in a baboon model. Forty-one survival and turnover measurements of (51)Crplatelets, (131)I-fibrinogen and (125)I-plasminogen in ten patients with aortofemoral knitted Dacron prostheses demonstrated platelet consumption after graft placement (platelet survival 4.2 days +/- 0.5 and turnover 68,000 plat/ul/day +/-10,000 compared with 8.2 days +/- 0.3 and 35,000 plat/ul/day +/- 5,000 respectively for control subjects with stable vascular disease, p < 0.01). In vitro platelet function test results were normal. Platelet consumption was interrupted by dipyridamole or a combination of dipyridamole and acetylsalicylic acid, and platelet survival normalized spontaneously during nine months postoperatively. No significantly increased consumption of fibrinogen or plasminogen was found in these patients with arterial grafts. Placement of impervious knitted Dacron velour aortic grafts in baboons reproduced platelet consumption that progressively normalized over six weeks postoperatively. Platelet survival measurements correlated directly with endothelial cell coverage of the graft luminal surface in these animals implying that endothelialization of the graft surface was also occurring postoperatively in patients.

Aged↗
PubMed1991

Force monitoring of clot retraction during DDAVP therapy for the qualitative platelet disorder of uraemia: report of a case.

The qualitative platelet disorder of uraemia results in decreased primary haemostatic capacity which can result in significant blood loss during invasive procedures. Treatments of the disorder tend to be empirical and include measures such as aggressive dialysis, conjugated oestrogens, and use of DDAVP. Improvement in platelet function is typically monitored by repeated bleeding times. The variability of the bleeding time is an all too recognized limitation of its usefulness. We report here the case of a 35-year old male with end stage renal disease who presented with intractable bleeding secondary to peptic ulcer disease and haemorrhagic gastritis. Platelet function tests including bleeding time, platelet aggregation studies, and clot retraction measurements were monitored before and after intravenous administration of DDAVP (0.3 microgram/kg). The bleeding time which had been 8 min before DDAVP did not change. Platelet aggregation studies revealed improved aggregation by both collagen and adenosine diphosphate. Clot retraction forces were dramatically enhanced after DDAVP. Pre-DDAVP clots containing 72 x 10(9) platelets per 1 and 1 g fibrinogen per 1 produced 90 dynes/cm2 of force at 800 s post-thrombin addition. Identical clots formed with blood drawn 2 h post-DDAVP produced 750 dynes/cm2. The DDAVP dose was repeated after 8 h with obvious slowing of blood loss. The marked effect of DDAVP on clot retraction may allow monitoring of DDAVP therapy utilizing this technique.

Adenosine Diphosphate↗
PubMed1992

Improved maintenance of platelet in vivo viability during storage when using a synthetic medium with inhibitors.

We report on the storage of platelet concentrates and the effects on in vivo and in vitro platelet function tests of adding the platelet inhibitors prostaglandin E1 and theophylline to a plasma-free synthetic medium and storage in containers with reduced surface-to-volume ratio. Paired in vivo studies on platelets labeled with indium 111 after 14-day storage demonstrated higher recoveries (mean +/- SD) of 23% +/- 9% and longer survivals of 109 +/- 59 hours for the test group versus 8% +/- 10% and 19 +/- 22 hours, respectively (p less than 0.01), for the control group (synthetic medium with no inhibitors and use of standard containers). The improved viability was associated with a significantly lower glycolytic rate; better maintenance of other in vitro parameters including respiratory activity, adenosine triphosphate levels, hypotonic shock response, surface glycoprotein Ib (by flow cytometry); and improved preservation of morphologic integrity (p less than 0.05). In particular, a strong inverse correlation (r = -0.91) was observed between in vivo recoveries and the fraction of platelets negative for glycoprotein Ib. We conclude that avoidance of platelet activation by a combination of inhibitors, plasma removal, and reduced container surface improves platelet respiratory activity, adenosine triphosphate and glycoprotein Ib levels, and posttransfusion viability of platelet concentrates stored for 14 days.

Adenosine Triphosphate↗
PubMed1995

Habitual diet, platelet function, fibrinogen and factor VII coagulant activity in young Finns.

OBJECTIVES: The objective of the study was to determine whether an association between diet and platelet function, plasma fibrinogen level and factor VII coagulant activity (VII:C) could be established in young subjects. DESIGN: Data on the habitual diet of the subjects were collected either by a questionnaire on food habits (n = 204) or by a 48-h dietary recall interview (n = 53). SUBJECTS: The subjects were participants in the project 'Cardiovascular Risk in Young Finns' (age range 15-30 years). A total of 204 subjects having a questionnaire on food habits participated in the platelet function tests and 53 also participated in a 48-h dietary recall interview. Plasma fibrinogen concentration and factor VII: C were measured from 79 subjects. MAIN OUTCOME MEASURES: Platelet function was tested by turbidometric measurement of platelet aggregation using ADP and collagen as aggregation agents. RESULTS: Platelet aggregation with ADP (at up to 4.0 mumol L-1) and collagen (at up to 5.0 micrograms mL-1 platelet-rich plasma PRP) showed that the diet characterized as 'saturated', i.e. containing high-fat milk and saturated fat, was associated with platelets less sensitive to aggregating agents in vitro when compared to the unsaturated type of diet. Collagen- but not ADP-induced aggregation decreased with age of the subjects (P = 0.026-0.057, regression coefficient). An inverse regression coefficient between plasma factor VII:C (101%; range 64-145%) and serum triglycerides (P = 0.006) and the intake of rye (g 1000 kcal-1; P = 0.03) were found. CONCLUSIONS: In this study we showed that platelet reactivity and factor VII:C already differ considerably between subjects at a young age, and diet may explain some of this variation.

Adolescent↗
PubMed2006

Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin.

INTRODUCTION: Aspirin is one of the most effective antiplatelet agents and is now commonly used to prevent vascular events. In some patients, however, recurrent vascular events have been demonstrated despite aspirin therapy. Our objective was to characterize individuals showing poor response to in vitro effect of aspirin, using PFA-100. METHODS: One hundred sixty-eight healthy male subjects were analyzed. We assessed platelet function tests, including PFA-100, whole blood aggregation, and optical platelet aggregation. Also measured were hemostatic and other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250 s with PFA-100 when incubated with 10 microM aspirin, whereas good responders were defined as having a CEPI-CT of more than 250 s. RESULTS AND CONCLUSIONS: PFA-100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%) were good responders (GR). Poor responsiveness was significantly associated with (1) higher basal platelet activities in PFA-100, as well as in whole blood aggregation and aggregometer;(2) increased level of adiponectin (8.8+/-4.1 micro g/mL [PR] vs 7.3+/-2.9 micro g/mL [GR], p=0.010);and (3) the presence of diabetes mellitus (17.5% [PR] vs 4.7% [GR], p=0.009). Importantly, whereas 24% of the subjects showed insufficient inhibition in PFA-100 when incubated with 10 microM aspirin, almost all subjects showed maximum inhibition with 30 microM aspirin. These observations suggest that higher doses of aspirin might overcome aspirin resistance.

Adiponectin↗
PubMed1980

Effects of oral contraceptives containing 50 microgram estrogen on blood coagulation in non-Caucasian women.

In one of the first longitudinal studies of 163 non-Caucasian women, comprehensive coagulation, fibrinolysis and platelet function tests were performed before and during 24 months of oral contraceptive pill usage containing 50 microgram estrogen. Results of this ongoing study indicate a state of abnormal coagulability with increase in fibrinogen, prothrombin, Factor V and Factor X. There was also a decrease in antithrombin III level. There was a shortening of overall clotting parameters measured by prothrombin time and Kaolin cephalin time. The significance of these changes in the aetiology of thromboembolism is discussed.

Asian People↗
PubMed1995

Platelet function analysis after in vitro treatment with hemostasis-affecting components.

An overall platelet function test in whole blood, which simulates conditions under arterial pressure, is useful in measuring the effect of polymer materials on blood hemostatic function. We performed biocompatibility tests with materials or plasma substitutes by interaction of blood from healthy volunteers and then subjected these blood samples to platelet function analysis (Thrombostat). We tested also the capacity of locally applied hemostatic agents for bleeding control by direct application of these agents onto the Thrombostat measuring cell. The biocompatibility tests with materials exposed to blood appeared very discriminating between compatible and noncompatible materials. The hemostatic capacity of blood exposed to noncompatible materials (assessed by binding of active thrombin) reduced markedly after one hour incubation of the material. The plasma substitutes did not affect hemostasis significantly. However, a blood dilution of 40%, as in cardiopulmonary bypass, increased the time required for closure of the measuring cell by a platelet plug exponentially. Local hemostatic agents could be selected according to their capacity to enhance platelet plug formation. In addition, ADP mixed with the hemostatic agent was most effective in improving capacity. We conclude that platelet function analysis contributes importantly to screening of materials and plasma substitutes with regard to their interaction with primary hemostasis.

Biocompatible Materials↗
PubMed1994

[Ex-vivo bleeding time as a control for platelet transfusion].

Thrombocytopenia is the most common cause of bleeding tendency and, if due to impaired platelet production, is best treated by platelet transfusion. For patients with acute leukemia prophylactic platelet transfusion should be considered if platelet count is below 20 x 10(9)/l. This will be underlined by a retrospective analysis at our clinic of 231 patients suffering from acute myelocytic leukemia (AML FAB M1-7) and showing an early-death rate of 7.7% by bleeding complications. To estimate the effectiveness of platelet transfusions, not only stopping of bleeding symptoms and corrected count increment (CCI) should be taken into account but also whether the patient has fever, sepsis, hepato-splenomegaly or has taken special drugs. Measuring the in vivo bleeding time is of little use for low reproduction and is stressing for patients. In 1985 Kratzer described a new and sensitive method for the evaluation of platelet function. After modifying this method it is now possible to test platelet function even with platelet counts below 50 x 10(9)/l.

Bleeding Time↗
PubMed2006

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.

Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

Assisted Circulation↗
PubMed2007

Drug insight: aspirin resistance--fact or fashion?

The term aspirin resistance has been used increasingly in clinical studies. The aim of this Review is to analyze the origin of this term, to discuss the biochemical, functional and clinical correlates of the phenomenon and to offer a conceptual framework to redefine the major determinants of variability between individuals in response to aspirin. Awareness needs to be increased of factors that might interfere with the desired antiplatelet effect of aspirin, particularly in terms of patients' adherence to treatment and avoidable drug interactions with some traditional NSAIDs. Gaining such knowledge could result in improved care of patients and might avoid the requesting of unnecessary platelet function tests of unproven clinical significance.

Aspirin↗
PubMed1984

[Blood platelet function following gamma globulin infusions in children with acute lymphatic leukemia during the remission-maintaining long-term therapy].

Platelet function tests prior to and post intravenous gammaglobulin infusions (i.v. IgG) were performed in 20 children with acute lymphoblastic leukemia under conventional maintainance therapy. Platelet function was not influenced in 8 patients with decreased preinfusion IgG-levels. Severe platelet function defects, resembling an acquired storage pool disease, post i.v. IgG-infusion, however, were observed in 2 of 12 patients with normal preinfusion IgG-levels.

Blood Platelets↗
PubMed1995

[Disorders of thrombocyte function as a cause of postoperative hemorrhage after tonsillectomy].

Tonsillectomies are the most frequently performed ENT surgical procedures and are potentially beset with a number of possible complications. Post-operative secondary hemorrhage still remains the most frequent complication despite improvements in surgical techniques and preoperative diagnostic evaluations. Besides unsuitable operative techniques, disturbances of circulation and wound infections, disturbances of hemostasis may play an important part. The objective of this paper was to examine the relative frequency of platelet functional disorders as a possible cause for secondary hemorrhage after tonsillectomies. In the past, most of these have been related to medication use. Eighty-nine patients were studied and historically showed no predisposition increased hemorrhage per se or in their families or gave reasons for other factors favoring secondary hemorrhage. The diminution or lack of collagen or ADP-induced agglutination served as an indication for a platelet functional disorder. Ten percent of the 89 patients experienced secondary hemorrhage, with platelet functional disorders proved in 40% of these patients. Because of these results a correlation was attempted between secondary hemorrhage and abnormal deficits of collagen and ADP-induced agglutinations in platelet functional tests, but this was not found. Necessary preoperative studies was attempted screening for hemostasis as well as medico-legal aspects connected with the prescription of medicines inhibiting platelet agglutination, especially use of acetylsalicylic acid before tonsillectomies, are discussed.

Adult↗
PubMed1998

[The O'Brien filter test in the differential diagnosis of disorders with high-grade thrombocytosis].

In the differential diagnosis of primary and secondary thrombocytosis, platelet function test can be used. We have examined the possible role of O'Brien's filter test in the differentiation of primary and secondary thrombocytosis in 53 patients with myeloproliferative diseases with primary thrombocytosis and in 21 patients with other disorders complicated by secondary thrombocytosis. By using heparin as an anticoagulant, the sensitivity of O'Brien's filter test proved to be 75%, and it's specificity was 85.7%. In blood samples anticoagulated with citrate, the sensitivity was 100% and specificity 83.3%. Based on these studies we suggest the use of O'Brien's filterometer as a screening test in the differential diagnosis in patients with elevated (> 400 x 10(9)/L) platelet count. In case of normal results, the causes of reactive thrombocytosis should be cleared first, while with pathologic results, haematological examination of the patients should be performed.

Chronic Disease↗
PubMed1982

Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis.

The efficacy of low-molecular-weight heparin as a prophylactic agent was assessed in 150 consecutive patients over the age of 40 undergoing major abdominal surgery. Fifty of these patients received 1250 activated partial thromboplastin time (APTT) units of low-molecular-weight heparin every 12 hours: three developed isotopic deep vein thrombosis, which was confirmed by phlebography in two cases. The other 100 patients received a single injection of 1850 APTT units of low-molecular-weight heparin. Three of them developed isotopic deep vein thrombosis; phlebography failed to confirm the presence of thrombi in each case. None of the 150 patients studied died from fatal or contributory pulmonary emboli. Low-molecular-weight heparin was not associated with any increase in preoperative or postoperative bleeding. The effect of equal amounts of postoperative bleeding. The effect of equal amounts of low-molecular-weight heparin and unfractionated heparin on the coagulation mechanism during surgery was investigated in another 30 patients. The clotting assays and results of in-vivo platelet function tests indicated that both preparations produced similar effect. Intragroup comparisons, however, showed significant differences in the anti-factor Xa activity, lipoprotein lipase release, and plasma prekallikrein concentrations. A single injection of low-molecular-weight heparin daily is a convenient way of preventing deep vein thrombosis in high-risk patients undergoing major abdominal surgery.

Adult↗
PubMed1989

Actin filament content in platelets--a sensitive index of cellular reactivity.

Blood platelets have the capacity to participate in a number of physiological as well as pathological processes within the circulation. In order to evaluate their cellular reactivity a number of platelet function tests have been developed. The main in vitro function tests are assessment of aggregation and adhesion, secretion, arachidonate metabolism, coagulant activities and the characterization of surface membrane glycoproteins (Day and Rao, 1986). Here we measure alterations of the G-/F-actin equilibrium of platelets. High F-actin values of unstimulated platelets indicate a hyperreactivity of the cell as examined in platelets from diabetics. Determination of the actin filament content in platelets can be considered as a new sensitive function test.

Actins↗
PubMed1985

Severe hemorrhagic tendency in heterozygous alpha 2-antiplasmin deficiency.

We report a case of partial deficiency of alpha 2-antiplasmin. A 45 year old Spanish man had a life long severe bleeding tendency after trauma. Routine coagulation and platelet functional tests in symptomatic and asymptomatic periods were normal. During the bleeding there was a rapid whole blood clot lysis and the concentration of alpha 2-antiplasmin in plasma was 20 to 25% of normal controls. After recovery these levels showed a slight increase (35 to 45% of normal). Addition of normal plasma to the patient's plasma increased alpha 2-plasmin inhibitor activity. Bidimensional electrophoresis of alpha 2-antiplasmin in the patient's plasma showed a normal pattern. Family studies showed that one of the proband's two sons had a mild hemorrhagic tendency and 40% of functional and antigenic levels of alpha 2-antiplasmin.

Blood Coagulation Factors↗