scholarly journals Evidence suggesting the regulation of a coagulation factor levels in rabbits by a transferable plasma agent

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 949-954
Author(s):  
EW Friedman ◽  
M Karpatkin ◽  
S Karpatkin

New Zealand white rabbits were given 30 ml of goat serum intravenously. This procedure resulted in an immediate decrease in platelet count, fibrinogen, and levels of coagulation factors II, V, VII, and X, due to consumption coagulopathy. These factors returned toward baseline levels approximately 12 hr after the injection. Plasma from rabbits who had received goat serum 48 hr previously (donor rabbits) was injected into recipient rabbits. This procedure resulted in a slight rise in the level of coagulation factor II (range, 20%-30%) and a significant rise in factors V (35%-75%), VII (35%-235%), and X (35%-75%) in the recipients. When plasma from control donor rabbits who had not received goat serum was injected into recipients, there was no change in these coagulation factors. It is postulated that the reduction in coagulation factor levels in donor rabbits induces a “coagulopoietin” for each factor or one “coagulopoietin” for all factors which stimulates increased synthesis and/or release of these factors in recipient rabbits.

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 949-954 ◽  
Author(s):  
EW Friedman ◽  
M Karpatkin ◽  
S Karpatkin

Abstract New Zealand white rabbits were given 30 ml of goat serum intravenously. This procedure resulted in an immediate decrease in platelet count, fibrinogen, and levels of coagulation factors II, V, VII, and X, due to consumption coagulopathy. These factors returned toward baseline levels approximately 12 hr after the injection. Plasma from rabbits who had received goat serum 48 hr previously (donor rabbits) was injected into recipient rabbits. This procedure resulted in a slight rise in the level of coagulation factor II (range, 20%-30%) and a significant rise in factors V (35%-75%), VII (35%-235%), and X (35%-75%) in the recipients. When plasma from control donor rabbits who had not received goat serum was injected into recipients, there was no change in these coagulation factors. It is postulated that the reduction in coagulation factor levels in donor rabbits induces a “coagulopoietin” for each factor or one “coagulopoietin” for all factors which stimulates increased synthesis and/or release of these factors in recipient rabbits.


1982 ◽  
Vol 47 (03) ◽  
pp. 218-220 ◽  
Author(s):  
P Sié ◽  
E Letrenne ◽  
C Caranobe ◽  
M Genestal ◽  
B Cathala ◽  
...  

SummaryIn order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and serum demonstrated that the levels of II rAg and of AT III, assessed by the Laurell technique with Behring antisera, were not reduced by the coagulation process. The patients were, a posteriori, classified into two groups according to the absence (group A) or the presence (group B) of factors predisposing to liver failure such as metastasis, cirrhosis, and prolonged shock. II rAg and AT III levels are significantly correlated; they are in the normal range in group A but reduced in group B. Thus II rAg or AT III level determinations are useful markers in the detection of liver failure associated to the consumption phenomenon. These results also suggest that part of the decreased AT III levels reported in severe cases of disseminated intravascular coagulation may be the consequence of an associated liver failure.


Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 219-231 ◽  
Author(s):  
R Egbring ◽  
W Schmidt ◽  
G Fuchs ◽  
K Havemann

To show whether direct proteolysis of coagulation factors may play a role in patients with so-called consumption coagulopathy, granulocytic neutral proteases in the plasma of patients with acute myelocytic leukemia and septicemia were assayed by one- and two-dimensional Laurell electrophoresis. Complexes between serum alpha1-antitrypsin and elastase-like granulocytic protease could be demonstrated in those patients with acute myelocytic leukemia and septicemia who also had moderate or severe coagulation defects. Despite the presence of a high antiprotease potential, addition of the elastase-like enzyme to normal plasma resulted in coagulation defects in vitro comparable to those seen in the patients. These results and the ability of the elastase- like protease to destroy isolated clotting factors suggested that in certain types of coagulation factor deficiencies direct proteolysis rather than consumption of clotting factors due to disseminated intravascular coagulation may be operational.


Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 219-231 ◽  
Author(s):  
R Egbring ◽  
W Schmidt ◽  
G Fuchs ◽  
K Havemann

Abstract To show whether direct proteolysis of coagulation factors may play a role in patients with so-called consumption coagulopathy, granulocytic neutral proteases in the plasma of patients with acute myelocytic leukemia and septicemia were assayed by one- and two-dimensional Laurell electrophoresis. Complexes between serum alpha1-antitrypsin and elastase-like granulocytic protease could be demonstrated in those patients with acute myelocytic leukemia and septicemia who also had moderate or severe coagulation defects. Despite the presence of a high antiprotease potential, addition of the elastase-like enzyme to normal plasma resulted in coagulation defects in vitro comparable to those seen in the patients. These results and the ability of the elastase- like protease to destroy isolated clotting factors suggested that in certain types of coagulation factor deficiencies direct proteolysis rather than consumption of clotting factors due to disseminated intravascular coagulation may be operational.


1979 ◽  
Author(s):  
B. Lacaze ◽  
C. Ferrand ◽  
O. Pepin

The intraperitoneal administration of the LD50 dose of Russell’s viper venom to Sprague Dawley rats induces a DIC with consumption coagulopathy. The PT, TT and APTT are increased and the recalcification time and platelet count is considerably decreased. Also the thromboelastogram is quite perturbed. In order to follow the modifications of the coagulation parameters induced by the venom in the presence and absence of Ticlopidine. Four groups of each eight animals are investigated : Control, Ticlopidine 150 mg/kg/d. P.O. 4 days, Venom LD5O of Russell’s venom viper (Sigma), i.e. 400 μg/kg by I.P. route, 15 hrs before sacrifice, Ticlopidine + Venom T. 150 mg/kq/d. P.O. 4 days and the LD50 venom 15 hrs before sacrifice. The venom showed versus control a significant increase of PT, and APTT a significant decrease of Recalcification time and platelet count. The prevention of the DIC by Ticlopidine is characterized by the normalization of the coagulation factors. In comparison with the venom the Ticlopidine group has an increase of rocalci-fication time and PT, TT, APTT and platelet count were identical with the control group. The fibrinogen level increase significantly. The histopathological examination of kidneys and lunqs show the characteristic lesions of DIC in the venom animals, and the protective activity of Ticlopidine versus the intravascular aggregats in the Ticlopidine venom group. No protection by Ticlopidine however, was shown against the neurotoxicity of the venom. The inhibition of platelet aggregats and the antithrombotic activity of a drug can be evaluated by this experimental model of an acute DIC.


1983 ◽  
Vol 50 (03) ◽  
pp. 749-752 ◽  
Author(s):  
Michael R Owens ◽  
Catherine D Cimino

SummaryA plasma factor, “coagulopoietin”, present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of “coagulopoietin” on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of. Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The “coagulopoietin” factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.


1963 ◽  
Vol 10 (02) ◽  
pp. 295-308 ◽  
Author(s):  
Clarence Merskey ◽  
Herbert Wohl

Summary1. Groups of rats were fed thrombogenic diets and the effects on blood coagulation and fibrinolysis assessed.2. Animals fed a diet containing cholesterol, thiouracil and cholic acid developed high levels of coagulation factors I, II, V, VII—X, VIII, IX and X.3. Animals fed a similar diet with additional 40% beef fat developed even greater elevation of V, VII—X, VIII and X, similar elevation of factor II, and lesser (but still significant) elevation of factors I and IX. In addition marked elevation of blood platelets occurred.4. Euglobulin lysis time of the group not fed the additional fat was longer than in controls. Significant prolongation of euglobulin lysis time was not found in the group fed additional fat.5. If the increased levels of plasma fibrinogen were taken into account, it was found that a larger amount of fibrin was lysed per unit time in the euglobulin lysis test with plasma from rats fed either atherogenic diet compared with controls.6. Defective thromboplastin generation was present in both groups of rats fed an atherogenic diet. The defect was present in the serum and was not due to lack of a factor required for thromboplastin generation. An inhibitor was present in the serum which was capable of preventing the action of normal serum.7. No good correlation was found between the occurrence of changes in blood coagulation or fibrinolysis and the presence or absence of thrombosis and infarction.8. The exact cause of these anomalies remains unexplained, as does the cause of the thrombosis in these animals. Starvation per se does not account for these abnormal findings. They could not adequately be explained on the basis of “hypercoagulability” of the blood.


1970 ◽  
Vol 23 (03) ◽  
pp. 593-600
Author(s):  
P Pudlák ◽  
I Farská ◽  
V Brabec ◽  
V Pospíšilová

Summary1. The following coagulation changes were found in rats with experimental hypersplenism: a mild prolongation of the recalcification time, shortened times in Quick’s test, a lowered activity in plasma thrombin time and shortened times in the partial thromboplastin test. Concentrations of factor II, V, VII (+X), VIII and X did not differ from those of normal control rats.2. The administration of adrenaline to hypersplenic rats induced the correction of the partial thromboplastin test, Quick’s test and plasma thrombin time to normal values. Concentrations of coagulation factors were not significantly changed. An increase was found in factor V.3. Splenectomy performed in hypersplenic rats was followed by a shortened recalcification time, a prolongation of the partial thromboplastin test and of the test with partial thromboplastin and kaolin. A prolongation was also observed in Quick’s test. Complete correction of plasma thrombin time was not observed. The concentration of factor VII increased.4. The administration of adrenaline to splenectomized rats with experimental hypersplenism did not induce any significant changes with the exception of a corrected plasma thrombin time and a decreased concentration of factor VIII.5. A different reaction of factor VIII to adrenaline in normal and hypersplenic rats is pointed out.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alberto Polimeni ◽  
Isabella Leo ◽  
Carmen Spaccarotella ◽  
Annalisa Mongiardo ◽  
Sabato Sorrentino ◽  
...  

AbstractCoronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, resulting in widespread microvascular thrombosis and consumption of coagulation factors. We conducted a meta-analysis in order to explore differences in coagulopathy indices in patients with severe and non-severe COVID-19. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases between December 2019 (first confirmed Covid-19 case) up to April 6th, 2020. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. Furthermore, results on additional coagulation parameters (platelet count, prothrombin time, activated partial thromboplastin time) were also analyzed. The primary analysis showed that mean d-dimer was significantly lower in COVID-19 patients with non-severe disease than in those with severe (SMD − 2.15 [− 2.73 to − 1.56], I2 98%, P < 0.0001). Similarly, we found a lower mean d-dimer in Survivors compared to Non-Survivors (SMD − 2.91 [− 3.87 to − 1.96], I2 98%, P < 0.0001). Additional analysis of platelet count showed higher levels of mean PLT in Non-Severe patients than those observed in the Severe group (SMD 0.77 [0.32 to 1.22], I2 96%, P < 0.001). Of note, a similar result was observed even when Survivors were compared to Non-Survivors (SMD 1.84 [1.16 to 2.53], I2 97%, P < 0.0001). Interestingly, shorter mean PT was found in both Non-Severe (SMD − 1.34 [− 2.06 to − 0.62], I2 98%, P < 0.0002) and Survivors groups (SMD − 1.61 [− 2.69 to − 0.54], I2 98%, P < 0.003) compared to Severe and Non-Survivor patients. In conclusion, the results of the present meta-analysis demonstrate that Severe COVID-19 infection is associated with higher D-dimer values, lower platelet count and prolonged PT. This data suggests a possible role of disseminated intravascular coagulation in the pathogenesis of COVID-19 disease complications.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.


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