Recurrent Venous Thrombosis Related To A Hereditary Dysfibrinogen With Abnormal Crossed Immunoelectrophoretic Pattern

1981 ◽  
Author(s):  
A C Papp ◽  
R M Snopko ◽  
E R Cole ◽  
R J Sassetti ◽  
K K Wu
Keyword(s):  
Venous Thrombosis ◽  
Relative Viscosity ◽  
Gravimetric Method ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
A Value ◽  
History Of ◽  
Abnormal Pattern ◽  
Recurrent Venous Thrombosis ◽  
Fibrinogen Molecule

A 24 year old man with a history of multiple recurrent venous thrombosis was found to have a qualitatively abnormal fibrinogen. Plasma fibrinogen concentration by a kinetic thrombin time method was 135mg% as compared to 150mg% by the gravimetric method of Ratnoff and Menzie. The thrombin, reptilase and Russell viper venom times were all approximately 50% longer than the normal values. Neither the thrombin time nor reptilase time was corrected upon addition of CaCl2. Antigenic quantitation by Laurell immunoelectrophoresis gave a value of 320mg%. On Ouchterlony immunodiffusion plate, the patient’s plasma and normal plasma showed a line of identity. The patient’s fibrinogen had a normal rate of migration by one-dimensional immunoelectrophoresis but it exhibited an abnormal pattern upon crossed immunoelectrophoresis. The abnormality is characterized by the presence of a shoulder on the anodal side of the fibrinogen peak. Family studies revealed that the fibrinogen defect was inherited as an autosomal dominant trait. To determine whether recurrent venous thrombosis is related to increased viscosity due to the abnormal fibrinogen, fibrinogen was purified by the method of BlombSck and the relative viscosity of fibrinogen solution was determined. Preliminary data were suggestive of an increased viscosity of the patient’s fibrinogen. These findings indicate that the immunologically abnormal dysfibrinogen may be responsible for recurrent venous thrombosis because of alteration of the physicochemical properties of the fibrinogen molecule.

The Prevalence of Hereditary Antithrombin-III Deficiency in Patients with a History of Venous Thromboembolism

1985 ◽  
Vol 54 (04) ◽  
pp. 744-745 ◽  
Author(s):  
R Vikydal ◽  
C Korninger ◽  
P A Kyrle ◽  
H Niessner ◽  
I Pabinger ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Antithrombin Iii ◽  
Positive Family History ◽  
Normal Range ◽  
The Family ◽  
History Of ◽  
Antithrombin Iii Deficiency ◽  
Recurrent Venous Thrombosis ◽  
Antithrombin Iii Activity ◽  
Slight Deficiency

SummaryAntithrombin-III activity was determined in 752 patients with a history of venous thrombosis and/or pulmonary embolism. 54 patients (7.18%) had an antithrombin-III activity below the normal range. Among these were 13 patients (1.73%) with proven hereditary deficiency. 14 patients were judged to have probable hereditary antithrombin-III deficiency, because they had a positive family history, but antithrombin-III deficiency could not be verified in other members of the family. In the 27 remaining patients (most of them with only slight deficiency) hereditary antithrombin-III deficiency was unlikely. The prevalence of hereditary antithrombin-III deficiency was higher in patients with recurrent venous thrombosis.

scholarly journals Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia [see comments]

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2194-2197
Author(s):  
C Demers ◽  
JS Ginsberg ◽  
P Brill-Edwards ◽  
A Panju ◽  
TE Warkentin ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Anticoagulant Therapy ◽  
Bleeding Episode ◽  
Heparin Therapy ◽  
Heparin Induced Thrombocytopenia ◽  
Normal Platelet ◽  
Reasonable Approach ◽  
History Of ◽  
Recurrent Venous Thrombosis ◽  
Phlegmasia Cerulea Dolens

In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin- induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.

scholarly journals Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia [see comments]

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2194-2197 ◽  
Author(s):  
C Demers ◽  
JS Ginsberg ◽  
P Brill-Edwards ◽  
A Panju ◽  
TE Warkentin ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Anticoagulant Therapy ◽  
Bleeding Episode ◽  
Heparin Therapy ◽  
Heparin Induced Thrombocytopenia ◽  
Normal Platelet ◽  
Reasonable Approach ◽  
History Of ◽  
Recurrent Venous Thrombosis ◽  
Phlegmasia Cerulea Dolens

Abstract In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin- induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.

A NEW THROMBOTIC DYSFIBRINOGENEMIA PRESENT IN SEVERAL MEMBERS OF A VENEZUELAN FAMILY

1987 ◽  
Author(s):  
C L Arocha Piñango ◽  
A Torres ◽  
R Marchi ◽  
S Rodríguez ◽  
H Camarillo ◽  
...  
Keyword(s):  
Protein C ◽  
Oral Anticoagulants ◽  
Clinical Signs ◽  
Immunological Methods ◽  
Thrombin Time ◽  
The Family ◽  
Mother And Daughter ◽  
History Of ◽  
Elevated Frequency ◽  
Fibrinogen Molecule

Up to the present, 16 dysfibrinogenemias have been described with thrombotic symptomatology, of which 3 cases showed low affinity of the fibrin for thrombin.In this study, we describe a family with an elevated frequency of thrombotic episodes which may be due to an alteration in the fibrinogen molecule causing a defective adsorption of thrombin by the fibrin formed.Two women, mother and daughter, were admitted to our clinic with a history of repeated pulmonary thromboembolisms. Coagulation studies (which included Antithrombin III, Protein C, etc.) revealed only a prolonged thrombin time with high fibrinogen levels (500 mg/dl) by the clot weight and immunological methods. More detailed studies on fibrinogen function showed:1) Abnormal monomers aggregation and polymerization rate, ho changes were observed in the latter when induced by reptilase followed by thrombin.2) Normal fibrinopeptide release3) Normal cross-linked and uncross-linked fibrin chains.4) Low affinity of fibrin for thrombin5) Normal plasmin degradation6) The electron microscopy showed a normal fibrin net with the characteristic periodic cross-striations pattern but which formed more slowly than normal.Both patients were treated with oral anticoagulants. The mother has not suffered any thromboembolic episodes in two years of treatment but the daughter has shown clinical signs of minor episodes of pulmonary thromboembolism which were confirmed by perfussion gammagraphy. In the family study, 4 members have died due to either venous or arterial thrombotic accidents. Fibrinogen function studies carried out on 8 members from 3 generations showed a prolonged thrombin time with delayed polymerization in 4 of the 8 (1 adult, 3 children), none of which have suffered any thrombotic manifestations up to the time of the study.The name of Caracas V is proposed for this new dysfibrino-genemia.

Action of Brinase on Human Fibrinogen and Plasminogen

1979 ◽  
Vol 42 (02) ◽  
pp. 571-581 ◽  
Author(s):  
Ph Vanhove ◽  
M B Donati ◽  
H Claeys ◽  
R Verhaeghe ◽  
J Vermylen
Keyword(s):  
Gel Filtration ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Promoting Effect ◽  
Human Fibrinogen ◽  
Parent Molecule ◽  
Elution Pattern ◽  
Fibrinogen Molecule

SummaryBrinase added to human plasma in vitro caused a decrease in fibrinogen concentration, positive paracoagulation tests and formation of a friable clot in sequence. Agarose gel filtration of these samples revealed the presence of fibrinogen derivatives both larger and smaller than the parent molecule. Infusion of the enzyme in vivo resulted in a decreased fibrinogen level, a prolonged thrombin time and an increase in fibrinogen related antigen (FRA) in serum. The elution pattern of FRA in the plasma samples obtained after infusion of Brinase was similar to that of the in vitro samples. The plasma pool of fibrinogen was partially consumed by infusion of Brinase, but the turnover of plasminogen remained unaffected. Purified plasminogen was partially degraded by addition of the enzyme but this was not accompanied by a generation of proteolytic activity. These findings confirm that Brinase induces a proteolytic degradation of fibrinogen in plasma without activation of the plasminogen-plasmin system. Exposure of polymerization site(s) in the fibrinogen molecule is probably responsible for the reported clot promoting effect of the enzyme.

scholarly journals Another Inherited Abnormality in Plasma Fibrinogen

1977 ◽  
Author(s):  
N. B. Bosch ◽  
C. L. Arocha-Piñango ◽  
A. Rodriguez ◽  
A. Ojeda ◽  
Z. Carvajal
Keyword(s):  
Ionic Strength ◽  
Electrophoretic Mobility ◽  
Factor Xiii ◽  
Polymerization Rate ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Fibrin Polymerization ◽  
History Of ◽  
Α Chain

A prolonged thrombin and reptilase time with normal fibrinogen concentration in a 9 — years old girl, with no history of bleeding, prompted us to study the behaviour of her fibrinogen. Thrombin and reptilase time in different conditions, immunolectrophoresis, immunodiffusion and fibrin polymerization were performed. The thrombin time was partially -corrected by calcium, ionic strength and increasing concentration of thrombin. Fibrin polymerization rate and monomer aggregation time were moderately abnormal. Immunodiffusion and immunoelectrophoresis showed lines of identity with the normal. The electrophoretic -mobility of the α β and γ fibrin chains was normal, but there was a large amount of α — chain left in the cross-linked fibrin,in the presence of factor XIII. The above results suggest the presence of another fibrinogen variant.

Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis

1987 ◽  
Vol 57 (02) ◽  
pp. 196-200 ◽  
Author(s):  
R M Bertina ◽  
I K van der Linden ◽  
L Engesser ◽  
H P Muller ◽  
E J P Brommer
Keyword(s):  
Liver Disease ◽  
Venous Thrombosis ◽  
Healthy Volunteers ◽  
Mean Value ◽  
Age Group ◽  
Normal Range ◽  
Heparin Cofactor Ii ◽  
History Of ◽  
Group 2 ◽  
Hereditary Nature

SummaryHeparin cofactor II (HC II) levels were measured by electroimmunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established.It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis.

Laboratory Evaluation and Clinical Characteristics of 2,132 Consecutive Unselected Patients with Venous Thromboembolism – Results of the Spanish Multicentric Study on Thrombophilia (EMET*-Study)

1997 ◽  
Vol 77 (03) ◽  
pp. 444-451 ◽  
Author(s):  
José Mateo ◽  
Artur Oliver ◽  
Montserrat Borrell ◽  
Núria Sala ◽  
Jordi Fontcuberta ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Odds Ratio ◽  
Protein C ◽  
Protein S ◽  
Laboratory Evaluation ◽  
Clinical Factors ◽  
Recurrent Thrombosis ◽  
Heparin Cofactor Ii ◽  
Crude Odds Ratio ◽  
History Of

SummaryPrevious studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2,132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinoge-nemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfib-rinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% Cl 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and in 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% Cl 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% Cl 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78,95% Cl 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.

Heparin Assays and Bleeding Complications in Treatment of Deep Venous Thrombosis with Particular Reference to Retroperitoneal Bleeding

1985 ◽  
Vol 53 (02) ◽  
pp. 278-281 ◽  
Author(s):  
H Asbjørn Holm ◽  
Ulrich Abildgaard ◽  
Sigmund Kalvenes
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Major Bleeding ◽  
Bleeding Complications ◽  
Minor Bleeding ◽  
Thrombin Time ◽  
Heparin Infusion ◽  
Retroperitoneal Bleeding ◽  
Heparin Activity ◽  
The Difference

SummaryBleeding complications occurred in 30 (11%) out of 280 patients who received continuous heparin infusion for deep venous thrombosis (DVT). 22 (8%) had minor while 8 patients (3%) had major bleeding complications (1 intrathoracic [fatal], 2 gastrointestinal and 5 retroperitoneal). Heparin activity, in daily drawn blood samples, was determined by four assays (chromogenic substrate [CS] assay, activated partial thromboplastin time [APTT], thrombin time with citrated plasma [CiTT] and thrombin time with recalcified plasma [CaTT]). The differences in median heparin activity between patients with minor bleeding and patients with no bleeding did not reach significance for any of the tests. In patients with major bleeding, the differences were significant with the CS (p = .011) and the CaTT (p = .030) assays. Patients with retroperitoneal bleeding had significantly increased median activity judged by all four assays: CS (p = .002), CaTT (p = .003), APTT (p = .010), CiTT (p = .029). The difference was most pronounced after four days of heparin treatment, but there was a considerable overlap with patients without bleeding.

EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

2019 ◽  
pp. 83-90
Author(s):  
Э.М. Гаглоева ◽  
В.Б. Брин ◽  
С.В. Скупневский ◽  
Н.В. Боциева ◽  
Т.В. Молдован
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Nickel Chloride ◽  
Activated Partial Thromboplastin Time ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

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