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

1981 ◽  
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.

Coagulation Disorders in Thrombocythaemia, a Study of Seven Cases

1962 ◽  
Vol 07 (01) ◽  
pp. 114-128 ◽  
Author(s):  
Stefan Niewiarowski ◽  
Halina Zywicka ◽  
Zbigniew Latałło
Keyword(s):  
Liver Parenchyma ◽  
Platelet Factor 4 ◽  
Coagulation System ◽  
Severe Bleeding ◽  
Clotting Factors ◽  
Platelet Factor ◽  
Antiheparin Activity ◽  
Thromboplastic Activity ◽  
Bleeding Episodes ◽  
Routine Coagulation

SummaryThe blood coagulation system has been studied in 7 patients with thrombocythaemia. 4 of these patients had thrombocythaemia after splenectomy, 2 of them had thrombocythaemia associated with myeloid leukemia, and 1 thrombocythaemia associated with polycythaemia. Severe bleeding episodes were noted in 5 cases, 2 patients had only mild bleeding symptoms.Each patient was examined several times. The period of observations varied from 2 months to 3 years. Platelet count varied from 350 000 to 3 800 000 per mm3.Bleeding time and tourniquet test were normal in all cases. Routine coagulation and fibrinolysis studies did not reveale characteristic abnormalities in plasma clotting factors. A decrease of prothrombin complex components was observed in 4 cases. This disturbance was due to the coexisting injury of liver parenchyma or myeloid changes but not to an increase of platelets or to the abnormalities in the platelet system.An increase of antiheparin activity was found in the plasma of 4 patients. This activity is probably due to the escape of platelet factor 4 from destroyed or qualitatively changed platelets into plasma.Platelet clotting factors were investigated in isolated platelet suspensions, A significant decrease of platelet factor 1 was observed in all patients and a decrease of platelet factor 4 in 5 patients. In 2 cases platelet factor 4 increased. Platelet thromboplastic activity showed a great variety of disturbances in conformity with other workers observations.Recent views on the pathogenesis of bleedings in thrombocythaemia are discussed. On the basis of their own investigations the authors suggest that the significant disturbances of platelet function may contribute to the development of bleeding, and that the increase of antiheparin activity in plasma may produce hypercoagulability and favorize the formation of thrombi.

Platelet Aggregation, β-Thromboglobulin and Platelet Factor 4 in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 236-239 ◽  
Author(s):  
J Fritschi ◽  
M Christe ◽  
B Lämmle ◽  
G A Marbet ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Aggregation ◽  
Discriminant Analysis ◽  
Plasma Levels ◽  
Platelet Activating Factor ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Aggregation Response ◽  
The Difference

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).

scholarly journals Release of endogenous chondroitin sulfate and heparin as consequence of dysregulated proteolysis in COVID-19

2021 ◽  
Author(s):  
Marco Ruggiero
Keyword(s):  
Adverse Effect ◽  
Platelet Aggregation ◽  
Chondroitin Sulfate ◽  
Plasma Proteins ◽  
Adverse Reactions ◽  
Proteolytic Enzymes ◽  
Protective Role ◽  
Platelet Factor ◽  
Sequential Release ◽  
Immune Mediated

Abstract Infection by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the pathogen responsible for COVID-19, is associated with immune-mediated responses that lead to dysregulated activation of proteolytic enzymes; these contribute to damage to the endothelium, thrombosis, hypercoagulability, and other hematologic complications that include thrombotic thrombocytopenia, a complication of severe COVID-19 as well as a potentially fatal adverse effect of COVID-19 vaccination. Here, it is demonstrated that proteolysis of plasma proteins leads to sequential release of endogenous glycosaminoglycans (GAGs), first chondroitin sulfate (CS), followed by heparin (HP). The extension and degree of what is called "proteolytic storm" determines whether only one endogenous type of GAGs (CS), or both (CS and HP), are released. Sulfated GAGs such as CS and HP exert a protective role against SARS-CoV-2 infection. However, sustained and excessive release of endogenous HP may be responsible for thrombotic thrombocytopenia just as it happens in HP-induced thrombocytopenia (HIT) a well-known side effect of HP administration that results in thromboembolisms in atypical sites, thrombocytopenia, and synthesis of autoantibodies directed against platelet factor 4 (PF4) that contribute to platelet aggregation. It is concluded that release of endogenous HP as consequence of dysregulated proteolysis occurring during COVID-19 or COVID-19 vaccination may play a fundamental role in the pathophysiology of the disease as well as in adverse reactions to vaccination.

scholarly journals In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 596-607
Author(s):  
J Musial ◽  
S Niewiarowski ◽  
LH Jr Edmunds ◽  
VP Jr Addonizio ◽  
KC Nicolaou ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Slow Component ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Specific Proteins ◽  
Monkey Plasma

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.

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

1995 ◽  
Vol 73 (01) ◽  
pp. 021-028 ◽  
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.

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

1970 ◽  
Vol 24 (01/02) ◽  
pp. 203-205 ◽  
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.

Plasma Concentrations of Platelet-Specific Proteins in Different Stages of Essential Hypertension: Interactions between Platelet Aggregation, Blood Lipids and Age

1985 ◽  
Vol 54 (02) ◽  
pp. 539-543 ◽  
Author(s):  
J Yamanishi ◽  
H Sano ◽  
K Saito ◽  
Y Furuta ◽  
H Fukuzaki
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Blood Lipids ◽  
Plasma Concentrations ◽  
Strong Positive Correlation ◽  
Platelet Factor ◽  
Hypertensive Group ◽  
Group A ◽  
Specific Proteins

SummaryPlasma β-thromboglobulin (βTG) and platelet factor 4 (PF4) were significantly higher in a group of 116 hypertensive men than in a normotensive group of 142 men. They increased with the stage of hypertension but the level did not correlate with the age of the subjects. Platelet aggregation was similar in the two groups and positively correlated with the age of the subjects in the normotensive group but not in the hypertensive group. A strong positive correlation was observed between the levels of plasma βTG and PF4 and between platelet aggregation to ADP and that to epinephrine in both the hypertensive and normotensive groups. However, there was no correlation between the level of plasma βTG or PF4 and platelet aggregation. Plasma antithrombin III was lower in the hypertensive group than in the normotensive group.These studies suggest that plasma levels of PTG and PF4 are closely related to the stage of hypertension and are better indicators than aggregation of in vivo platelet activation in hypertensive subjects. Enhanced platelet activation may be involved in the acceleration of hypertensive arteriovascular damage and atherosclerosis.

Standardization of β-Thromboglobulin and Platelet Factor 4: A Collaborative Study to Investigate the Sources and Extent of Variation in the Measurement of Platelet Specific Proteins

1983 ◽  
Vol 50 (03) ◽  
pp. 686-689 ◽  
Author(s):  
A D Curtis ◽  
P J Kerry
Keyword(s):  
Collaborative Study ◽  
Platelet Factor 4 ◽  
Plasma Samples ◽  
Significant Component ◽  
Platelet Factor ◽  
Specific Proteins

SummaryA collaborative study involving seven laboratories has been carried out to investigate the sources and extent of variation in the measurement by radioimmunoassay of β-thromboglobulin (β-TG) and platelet factor 4 (PF4). Three plasma samples, one purified β-TG sample and two purified PF4 samples were assayed against house standards for the respective antigens by each laboratory.The main source of variation of both β-TG and PF4 measurements was inter-assay (particularly for PF4). It was found that a significant component of this variation was due to the participants’ use of different preparations as house standards for β-TG and for PF4. This indicates that the first step in the standardization of β-TG and PF4 measurement should be the introduction of a reference for each.

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