Effects of piretanide on plasma fibrinolytic activity, platelet aggregation and platelet factor-4 release in man

SummaryWe have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. β-Thromboglobulin (β-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of β-TG and the stages of either retinopathy or macroangiopathy or nephropathy. The difference is more marked between normals and diabetics with neuropathy (p = 0.026). The aggregation response to ADP and platelet activating factor (PAF) is enhanced at lower stimulator concentration. Using the β-TG, PF4 and aggregation values the discriminant analysis allows a distinction of several subgroups especially with nephropathy and neuropathy (Table 6).

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Antibodies to Macromolecular Platelet Factor 4-Heparin Complexes in Heparin-induced Thrombocytopenia: a Study of 44 Cases

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651670 ◽

1995 ◽

Vol 73 (01) ◽

pp. 021-028 ◽

Cited By ~ 189

Author(s):

J Amiral ◽

F Bridey ◽

M Wolf ◽

C Boyer-Neumann ◽

E Fressinaud ◽

...

Keyword(s):

Molecular Weight ◽

Platelet Aggregation ◽

Early Diagnosis ◽

Healthy Subjects ◽

Platelet Factor 4 ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Sulphated Polysaccharides ◽

Major Interest ◽

Heparin Complexes

SummaryAs heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 <0.3) and 35 patients with other causes of thrombocytopenia (A492 <0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 ± 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped ≤ 100 × 109/l only at days 11–12. Surprisingly, among 41 patients under heparin for >7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.

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Platelet Factor 4 (PF4) Release during Human Platelet Aggregation in Diabetic Patients

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654225 ◽

1970 ◽

Vol 24 (01/02) ◽

pp. 203-205 ◽

Cited By ~ 9

Author(s):

J Chmielewski ◽

R Farbiszewski

Keyword(s):

Diabetes Mellitus ◽

Platelet Aggregation ◽

Essential Role ◽

Human Platelet ◽

Platelet Factor 4 ◽

Diabetic Patients ◽

Thromboembolic Complications ◽

Platelet Factor ◽

Human Platelet Aggregation

SummaryThe release of platelet factor 4 during platelet aggregation was investigated in diabetic patients. We observed an increased release of platelet factor 4 in diabetic patients.The authors suggest that the increased release of platelet factor 4 may play an essential role in pathogenesis of thromboembolic complications in diabetes mellitus.

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Beta - ThrombogloBulin And HA - Platelet Factor 4 In Multiple Myeloma, Hodgkin Disease And Malig - Nant Lymphoma - Effects Of Therapy

10.1055/s-0038-1653332 ◽

1981 ◽

Cited By ~ 1

Author(s):

H G Klingemann ◽

R Eqbrinq ◽

K Havemann

Keyword(s):

Multiple Myeloma ◽

Platelet Aggregation ◽

Malignant Lymphoma ◽

Proteolytic Enzymes ◽

Platelet Factor 4 ◽

Hodgkin Disease ◽

In Vitro Tests ◽

Clotting Factors ◽

Platelet Factor ◽

Specific Proteins

Determination of platelet specific proteins Beta-Thromboglobulin ( β-TG) and High Affinity Platelet Factor 4 (PF 4) in plasma has been proved as useful marker for an enhanced release reaction in some diseases, mostly due to an in - creased platelet aggregation. To evaluate suit - able marker for a prethrombotic state in some myeloproliferative diseases ue investigated patients suffering from multiple myeloma, Hodgkin disease and malignant lymphoma. β- TG and PF 4 were measured in platelet poor plasma using RIA - kits (Amersham-Buchler / Abbott Labor.). In addition ue determined; platelet count, spontaneous and collagen induced platelet aggregation, the activity of AT III and of the clotting factors I, V, VIII, XIII and the concentration of FDP.RESULTS: Normal range was found to be 0-55 ng/ml forβ-TG and 0-12 ng/ml for PF 4. Both release proteins were increased in 17 out of 25 patients with myeloma, in 13 out of 15 patients with Hodgkin disease and in 10 out of 12 patients with malignant lymphoma. A correlation to the severity of the diseases were demonstrable. Chemotherapy caused a decrease of β -TG and PF 4 levels in some cases. However no correlation could be found between β- TG and PF 4 levels and in vitro tests of platelet aggregation. Further clotting assay provided evidence for an activation of clotting (like DIC) in a few patients. Other possibilities - like the release of the platelet specific proteins by immunocomplexes, prostaglandins or proteolytic enzymes from granulocytes must taken into account.

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The Platelet Aggregation Score and Its Correlation to β- Thromboglobulin and Platelet Factor 4 Levels

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969500100206 ◽

1995 ◽

Vol 1 (2) ◽

pp. 135-141 ◽

Cited By ~ 8

Author(s):

Svetlana Kaplan ◽

Alexander Kaplan ◽

Karen F. Marcoe ◽

Gerge O. Gey ◽

Harvey Schiller ◽

...

Keyword(s):

Platelet Aggregation ◽

Platelet Factor 4 ◽

Platelet Factor

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The interaction of platelets with aortic subendothelium: inhibition of adhesion and secretion by prostaglandin I2

Blood ◽

10.1182/blood.v58.2.198.198 ◽

1981 ◽

Vol 58 (2) ◽

pp. 198-205 ◽

Cited By ~ 42

Author(s):

B Adelman ◽

MB Stemerman ◽

D Mennell ◽

RI Handin

Keyword(s):

Platelet Aggregation ◽

Aortic Wall ◽

Ex Vivo ◽

Rabbit Aorta ◽

Platelet Factor 4 ◽

Direct Immunofluorescence ◽

Balloon Injury ◽

Prostaglandin I2 ◽

Platelet Factor ◽

Reduced Surface

Abstract We have studied the effect of prostaglandin I2 on platelet turnover, attachment to the subendothelium, and secretion following balloon deendothelialization of the rabbit aorta. Survival of 51Cr-labeled platelets in the balloon-injured animals remained normal. Thirty minutes after injury, there were 4.52 X 10(6) platelets/sq cm attached to the aortic surface, which was 87% covered by platelets. Although plasma platelet factor 4, as measured by radioimmunoassay, did not rise above the normal level of 6.8 +/- 2.6 ng/ml (mean +/- SEM) during the first hour after balloon injury, platelet factor 4 antigen was detected within the vessel wall by direct immunofluorescence within 30 min of injury. An infusion of 650–850 ng/kg/min prostaglandin I2 completely inhibited platelet aggregation and reduced surface coverage by 84% and platelet attachment by 63%. Animals given 50–100 ng/kg/min prostaglandin I2, which only partially inhibited platelet aggregation, had 70% of the aortic surface covered by platelets. Platelet factor 4 antigen was also detected within the aortic wall. Platelet attachment was normal in animals that had been given 850 ng/kg/min prostaglandin I2 prior to balloon injury but sacrificed after the infusion was stopped and ex vivo platelet aggregation had returned to normal.

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