scholarly journals Cold-induced contact surface activation of the prothrombin time in whole blood

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 38-42
Author(s):  
RN Palmer ◽  
HR Gralnick
Keyword(s):  
Prothrombin Time ◽  
Whole Blood ◽  
Room Temperature ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor Xii ◽  
Contact Phase ◽  
Fletcher Factor ◽  
Esterase Inhibitor

Studies of the prothrombin time (PT) have revealed that contact with borosilicate or commercial siliconized borosilicate markedly shortens the PT. This shortening is related to the activation of the contact phase of blood coagulation. This shortening of the PT occurs in both normal whole blood and plasma when stored in borosilicate or siliconized borosilicate tubes at 4 degree C and to a lesser degree at room temperature. Studies indicated the importance of several coagulation factors in decreasing the PT. The PT did not change in blood deficient in factor XII or in plasma deficient in Fletcher factor or high molecular weight kininogen, while blood deficient in CI esterase inhibitor (CI INH) had the most profound shortening. Shortening of the PT correlated directly with increased levels of factor VII. When purified CI INH was added to normal blood, it markedly reduced the activation of factor VII and the shortening of the PT in a dose-related manner. These studies indicate the pivotal roles of the contact phase of coagulation in initiating activation of the PT and of CI INH in inhibiting the activation of the coagulation factor(s) responsible for the cold-promoted activation of factor VII.

scholarly journals Cold-induced contact surface activation of the prothrombin time in whole blood

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 38-42 ◽  
Author(s):  
RN Palmer ◽  
HR Gralnick
Keyword(s):  
Prothrombin Time ◽  
Whole Blood ◽  
Room Temperature ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor Xii ◽  
Contact Phase ◽  
Fletcher Factor ◽  
Esterase Inhibitor

Abstract Studies of the prothrombin time (PT) have revealed that contact with borosilicate or commercial siliconized borosilicate markedly shortens the PT. This shortening is related to the activation of the contact phase of blood coagulation. This shortening of the PT occurs in both normal whole blood and plasma when stored in borosilicate or siliconized borosilicate tubes at 4 degree C and to a lesser degree at room temperature. Studies indicated the importance of several coagulation factors in decreasing the PT. The PT did not change in blood deficient in factor XII or in plasma deficient in Fletcher factor or high molecular weight kininogen, while blood deficient in CI esterase inhibitor (CI INH) had the most profound shortening. Shortening of the PT correlated directly with increased levels of factor VII. When purified CI INH was added to normal blood, it markedly reduced the activation of factor VII and the shortening of the PT in a dose-related manner. These studies indicate the pivotal roles of the contact phase of coagulation in initiating activation of the PT and of CI INH in inhibiting the activation of the coagulation factor(s) responsible for the cold-promoted activation of factor VII.

The Prothrombin Time: The Mechanism Of In Vitro Activation

1981 ◽  
Author(s):  
R Palmer ◽  
H Gralnick
Keyword(s):  
Prothrombin Time ◽  
Whole Blood ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Factor Vii ◽  
Normal Blood ◽  
Factor Xii ◽  
Contact Activation ◽  
In Vitro Activation

We have described shortening of the prothrombin time (PT) when blood is collected in borosilicate or siliconized boro- silicate tubes. The shortening is time dependent and occurs more rapidly at 4° C than at room temperature. We have studied the mechanisms of in vitro activation of the PT utilizing normal blood and blood congenitally deficient in coagulation factors. We have found that the blood deficient in factor XI has the same rate of shortening of the PT as in normal blood, while blood deficient in factor IX has only 50/ that of normal and factor XII deficient blood does not have any in vitro activation. The blood deficient in Cl INH ihas the most severe shortening of the PT.Analysis of the coagulation factors affected during the in vitro activation of normal blood revealed that factor VII-X is increased and this is related primarily to factor VII activation. In borosilicate factor V did not change, factor IX decreased by 15-20% while factor XII showed no change in the assay system. The activation can be totally blocked by addition of Cl INH or corn trypsin inhibitor (specific inhibitor of XII activation) to whole blood. These studies indicate that the PT is shortened in vitro by at least two mechanisms of activation of whole blood: 1) factor XII is activated by surface contact with siliconized borosilicate or borosilicate and in turn, directly activates factor VII; 2) factor XIIa activates prekallikrein to kalli- krein which in turn activates factor IX. Factor IXa then activates factor VII and it would appear that approximately one-half of the activation of the PT is directly through this pathway. Inhibitors of factor XII activation, Cl INH and CFI can totally inhibit the activation in vitro. Thus, surface activation of factor XII is the pivotal reaction in the in vitro shortening of the PT in whole blood. These studies allow new strategies for the prevention of in vitro activation of the PT, and may allow for more precise measurement of the PT without concern for contact activation by the use of specific inhibitors.

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

2004 ◽  
Vol 92 (09) ◽  
pp. 503-508 ◽  
Author(s):  
Hans-Ulrich Pauer ◽  
Thomas Renné ◽  
Bernhard Hemmerlein ◽  
Tobias Legler ◽  
Saskia Fritzlar ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Mendelian Inheritance ◽  
Biological Role ◽  
Factor Xii ◽  
Wild Type ◽  
Contact Phase ◽  
Health And Disease

SummaryTo analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII-/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII-/- mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII-/- males and FXII-/females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII-/females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII-/mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII-/mice will be helpful to elucidate the biological role(s) of FXII in health and disease.

Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy

2011 ◽  
Vol 114 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Karén Matevosyan ◽  
Christopher Madden ◽  
Samuel L. Barnett ◽  
Joseph E. Beshay ◽  
Cynthia Rutherford ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Scientific Data ◽  
Factor Vii ◽  
Plasma Transfusion ◽  
Transfusion Therapy ◽  
Study Results ◽  
Neurosurgical Patients ◽  
Transfusion Guidelines

Object Neurosurgical patients often have mildly prolonged prothrombin time (PT) or international normalized ratio (INR). In the absence of liver disease this mild prolongation appears to be due to the use of very sensitive PT reagents. Therefore, the authors performed relevant coagulation factor assays to assess coagulopathy in such patients. They also compared plasma transfusion practices in their hospital before and after the study. Methods The authors tested 30 plasma specimens from 25 patients with an INR of 1.3–1.7 for coagulation factors II, VII, and VIII. They also evaluated plasma orders during the 5-month study period and compared them with similar poststudy periods following changes in plasma transfusion guidelines based on the study results. Results At the time of plasma orders the median INR was 1.35 (range 1.3–1.7, normal reference range 0.9–1.2) with a corresponding median PT of 13.6 seconds (range 12.8–17.6 seconds). All partial thromboplastin times were normal (median 29.0 seconds, range 19.3–33.7 seconds). The median factor VII level was 57% (range 25%–124%), whereas the hemostatic levels recommended for major surgery are 15%–25%. Factors II and VIII levels were also within the hemostatic range (median 72% and 118%, respectively). Based on these scientific data, plasma transfusion guidelines were modified and resulted in a 75%–85% reduction in plasma orders for mildly prolonged INR over the next 2 years. Conclusions Neurosurgical patients with a mild prolongation of INR (up to 1.7) have hemostatically normal levels of important coagulation factors, and the authors recommend that plasma not be transfused to simply correct this abnormal laboratory value.

scholarly journals Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients—A Single-Center Experience in Genetic Diagnosis

2021 ◽  
Vol 10 (2) ◽  
pp. 347
Author(s):  
Barbara Preisler ◽  
Behnaz Pezeshkpoor ◽  
Atanas Banchev ◽  
Ronald Fischer ◽  
Barbara Zieger ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Single Gene ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Molecular Genetic Analysis ◽  
Factor Vii ◽  
Factor Xii ◽  
Activity Levels

Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.

scholarly journals The activation of the contact phase of coagulation by physiologic surfaces in plasma: the effect of large negatively charged liposomal vesicles

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1525-1533 ◽  
Author(s):  
KA Mitropoulos ◽  
JC Martin ◽  
BE Reeves ◽  
MP Esnouf
Keyword(s):  
Fatty Acid ◽  
Contact Surface ◽  
Negative Charge ◽  
Sodium Stearate ◽  
Late Pregnancy ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor Xii ◽  
Contact Phase ◽  
Lipoprotein Particles

Abstract The endogenous, negatively charged surface that induces activation of the contact coagulation factors was investigated in plasmas taken from women in late pregnancy and control subjects of child-bearing age. The plasmas from the two groups of subjects were incubated at 4 degrees C for 24 hours either in plastic or in glass tubes and the factor VII coagulant activity (VIIc) was assayed in the treated plasmas. The activation of factor VII under these conditions involves the generation of enzymes derived from factor XII (XIIa). The contact surface is rate- limiting for the activation of factor VII in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge. The size of these vesicles is within the range of sizes of the large lipoprotein particles (chylomicrons, very low and intermediate-density lipoproteins). The relationship between the density of negative charge on the liposomal vesicles and VIIc was similar in the late pregnancy and the control plasmas incubated in plastic tubes. At a saturating density of negative charge the observed relative VIIc was similar in both sets of plasmas. The incubation of late pregnancy or control plasma in plastic tubes in the presence of sodium stearate caused VIIc to increase with increasing concentration of the added fatty acid. These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor XIIa and the subsequent activation of factor VII. Moreover, plasmas from women in late pregnancy have a higher concentration of potential surface and a higher density of negative charge than the plasmas from nonpregnant women.

scholarly journals The activation of the contact phase of coagulation by physiologic surfaces in plasma: the effect of large negatively charged liposomal vesicles

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1525-1533
Author(s):  
KA Mitropoulos ◽  
JC Martin ◽  
BE Reeves ◽  
MP Esnouf
Keyword(s):  
Fatty Acid ◽  
Contact Surface ◽  
Negative Charge ◽  
Sodium Stearate ◽  
Late Pregnancy ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor Xii ◽  
Contact Phase ◽  
Lipoprotein Particles

The endogenous, negatively charged surface that induces activation of the contact coagulation factors was investigated in plasmas taken from women in late pregnancy and control subjects of child-bearing age. The plasmas from the two groups of subjects were incubated at 4 degrees C for 24 hours either in plastic or in glass tubes and the factor VII coagulant activity (VIIc) was assayed in the treated plasmas. The activation of factor VII under these conditions involves the generation of enzymes derived from factor XII (XIIa). The contact surface is rate- limiting for the activation of factor VII in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge. The size of these vesicles is within the range of sizes of the large lipoprotein particles (chylomicrons, very low and intermediate-density lipoproteins). The relationship between the density of negative charge on the liposomal vesicles and VIIc was similar in the late pregnancy and the control plasmas incubated in plastic tubes. At a saturating density of negative charge the observed relative VIIc was similar in both sets of plasmas. The incubation of late pregnancy or control plasma in plastic tubes in the presence of sodium stearate caused VIIc to increase with increasing concentration of the added fatty acid. These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor XIIa and the subsequent activation of factor VII. Moreover, plasmas from women in late pregnancy have a higher concentration of potential surface and a higher density of negative charge than the plasmas from nonpregnant women.

Analysis of Children with Coagulation Test Abnormality in Pre-Surgical Evaluation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4080-4080
Author(s):  
Seung Yeon Kwon ◽  
Jung Woo Han ◽  
Sung Chul Won ◽  
Jaewoo Song ◽  
Chuhl Joo Lyu
Keyword(s):  
Surgical Procedures ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor Xii ◽  
Surgical Evaluation ◽  
Bleeding History ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Prothrombine time (PT) and activated prothrombine time (aPTT) are common tests used for screening of coagulation function before surgical procedures. We analyzed underlying causes of abnormal coagulation test results which were incidentally found during pre-surgical evaluation in healthy patients without definite bleeding history. Total 58 children referred to pediatric hematoloy service for abnormal PT and aPTT results in pre-surgical evaluation between June 2006 and May 2008 were analyzed retrospectively by review of medical records. 50 patients showed aPTT prolongation, 5 patients PT prolongation, 2 patients PT and aPTT prolongation and another three patients showed normal PT and aPTT. Among 55 patients with abnormal results, 25 patients (43%) were recovered spontaneously during their follow up tests, 17 patients (29%) showed lower level of certain coagulation factor than reference range and the other 13 patients were lost during follow up despite of recommendation for further evaluation. Mean value of international normalized ratio (INR) for PT and aPTT of the patients recovered spontaneously were 1.05±0.11, 44.53±5.01seconds(s), and 1.12±0.11, 47.0±5.36s in patients with lower level of coagulation factor, showing significant increase of PTT in patients with lower factor levels (p<0.05). Median time required for spontaneous recovery was four weeks and 18 patients (72%) were recovered within this time. Among 17 patients with lower level of certain coagulation factor then reference level, there were 11 patients with low factor XII level, three patients with low factor VIII level, three patients with low von Willebrand factor, two patients each for low factor VII and factor XI and one patient with low factor V level. Among them three patients with low level in von Willebrand factor, one patient with low factor VII and two patients with low factor XI showed deficient level of coagulation factors requiring factor replacement for the surgical procedures. From this analysis of patients with incidentally found PT or aPTT prolongation, 43% of patients were spontaneously recovered during follow up period within 4 weeks in median. However, we also found that 29% of patients had relatively lower level of coagulation factor than reference range. Even though most of them were factor XII decrease which is not closely related with bleeding tendency, six patients had significant deficiencies of coagulation factors requiring factor replacement during surgical procedures. These results suggest that we should keep following up and undergo adequate evaluation for underlying coagulation factor deficiencies in patients who have sustaining PT and aPTT prolongation abnormalities despite of absence of any bleeding history.

A hitherto undescribed plasma factor acting at the contact phase of blood coagulation (Flaujeac factor): case report and coagulation studies

Blood ◽  
1975 ◽  
Vol 46 (5) ◽  
pp. 761-768 ◽  
Author(s):  
MJ Lacombe ◽  
B Varet ◽  
JP Levy
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factor ◽  
Old French ◽  
Bleeding Tendency ◽  
Contact Phase ◽  
Hageman Factor ◽  
Coagulation Defect ◽  
Plasma Factor ◽  
Fletcher Factor

Abstract This paper reports an asymptomatic coagulation defect responsible for an abnormality at the contact phase of blood coagulation in vitro, distinct from Hageman factor and Fletcher factor deficiencies. Coagulation studies in a 50-yr-old French woman without bleeding tendency revealed the following results: whole-blood clotting time in glass tubes and activated partial thromboplastin time with kaolin and ellagic acid were greatly prolonged; one-stage prothrombin was normal; no circulating anticoagulant was detected, and the infusion of normal plasma corrected the coagulation defect with an estimated half-life of 6.5 days; the levels of factor VIII, IX, XI, and XII were normal; mutual correction was obtained with a Fletcher factor-deficient plasma; the level of whole complement was normal. Studies of the contact phase of blood coagulation and contact-induced fibrinolysis showed the same abnormalities as in Hageman factor- and Fletcher-deficient plasmas. These results indicate that the patient's plasma is deficient in a previously undescribed coagulation factor, which participates in the initial stage of the blood coagulation process in vitro. Family studies revealed consanguinity in the propositus' parents. The assay of this newly described factor in the propositus' children revealed a partial defect, compatible with a heterozygous state, in three of the four tested children. This indicates a recessive inheritance of this new blood coagulation defect.

Thromboelastography in Children with Coagulation Factor Deficiencies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2139-2139 ◽  
Author(s):  
Meera B. Chitlur ◽  
Indira Warrier ◽  
Madhvi Rajpurkar ◽  
Wendy Hollon ◽  
Lolita Llanto ◽  
...  
Keyword(s):  
Whole Blood ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Response To Treatment ◽  
Factor Vii ◽  
P Value ◽  
Factor V ◽  
Mean Values ◽  
Significant Difference

Abstract The thromboelastograph produces a continuous profile of the rheological changes that occur during the process of coagulation using whole blood. This information can be transformed into a dynamic velocity profile of the changes in blood elasticity occurring during clotting. We used the TEG® hemostasis analyzer in patients with hemophilia A or B with and without inhibitors and other coagulation factor deficiencies (OFD), to study the thromboelastographic profiles in these patients. Materials and Methods: 62 children (6 months-19 years old) were enrolled according to IRB regulations. 29 children had severe hemophilia A (SHA), 4 moderate hemophilia A or B (Mod.H), 2 severe factor VII deficiency, 1 combined factor V and VIII deficiency, 1 VWD (type II B), 1 severe factor V deficiency, 1 Severe PAI deficiency, 19 normal controls (NC), and 4 SHA with inhibitors (SHA+I). All patients were studied 72 hours after the last dose of factor. Citrated whole blood was activated using recombinant human tissue factor (Innovin, Dade Behring Inc®) and recalcified using 0.2M CaCl2. In patients with central lines with heparin, a heparinase cup was used. The TEG® was run for ≥ 90 min. CBC with differential was obtained on all subjects. Results: There was no significant difference in the CBC parameters among patients. Analysis of the TEG data revealed the following: Table 1 TEG Parameters (mean values) SHA (n=29) Mod.H (n=4) SHA+I (n=4) OFD (n=6) Control(n=19) MTG:Max rate of thrombin generation; TMG: Time to MTG; R: Reaction Time; K: Time to reach an amplitude of 20mm; MA: Max. Amplitude MTG(mm*100/sec) 8.7 9.6 1.3 9 17 TMG(min) 27.5 16.6 62.7 17.5 8.9 R(min) 22 14 56 15 7 K(min) 7 4 41 4 2 Max.Amplitude, MA (mm) 59 56 12 58 62 The rate of thrombin generation as visualized by plotting the 1st derivative of the TEG course, in patients with SHA without inhibitors, showed that they could be divided into 2 groups based on MTG (</>9). When analysed the 2 groups showed the following characteristics (5 representative curves from each group are shown): Figure Figure Table 2 TEG Parameters (Mean values) MTG < 9 (n=16) MTG > 9 (n=13) p value TMA: Time to MA; MTG(mm*100/sec) 5.5 12.6 <0.001 TMG (min) 33 20 0.009 R(min) 26 16 0.004 K(min) 9 3.4 0.03 MA(mm) 56.1 62.3 0.01 TMA(min) 60 38 0.006 13/29 children with SHA had target joints and 69%of patients with target joints had a MTG<9. Conclusions: SHA patients have variable bleeding tendencies as seen by the variation in MTG. A lower MTG is associated with a higher incidence of target joints. This may provide a clue as to which patients may have the greatest benefit from primary prophylaxis. Patients with OFD have a TEG® profile similar to Mod.H patients. SHA+I have poor thrombin generation as seen by a significantly longer TMG and R time (p <0.05), compared to all subjects. The TEG may provide valuable clues to the severity of bleeding tendencies in patients with factor deficiencies. In additional observations (not shown), it appears that the TEG may be used to monitor the response to treatment with factor concentrates and tailor treatment with rFVIIa.

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