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 ◽  
...  

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.

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 38-42 ◽  
Author(s):  
RN Palmer ◽  
HR Gralnick

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.


Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 38-42
Author(s):  
RN Palmer ◽  
HR Gralnick

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.


2020 ◽  
Vol 4 (2) ◽  
pp. 1048-1056
Author(s):  
F.N. Karpenko ◽  
◽  
A.V. Novik ◽  
E.D. Rasyuk ◽  
V.V. Pasyukov ◽  
...  

The article presents an analysis of the modern approach to the treatment of acute obstetric hemorrhage. Some features of the preparation of leukodepleted and pathogen-reduced blood components are shown and indications for use in severe obstetric blood loss are determined. It has been shown that the pathogen reduction of blood components leads to a decrease the level of coagulation factors (coagulation factor VIII, fibrinogen in fresh frozen plasma) by 20-30 %, the activity and number of platelets by 15-20 % in platelet concentrate, does not affect the morphological usefulness of platelets. A "package" of blood components for the provision of emergency transfusion therapy for obstetric bleeding has been calculated. The need for a given quantity of blood components was determined – 2.3 "packages" per 1000 births. The proposed "emergency obstetric care packages" and the organization of their centralized delivery to medical healthcare organizations ensure a high degree of readiness of the blood service to comply with the "golden hour" rule for treating acute severe obstetric hemorrhage and minimize post-transfusion reactions and complications when using them. Pathogen-reduced blood components are expensive. Therefore, their use in clinical practice is indicated for the decreed contingents of recipients: for organ and tissue transplantation, in neonatology, oncohematology and for recipients with “multiple transfusions of blood, its components”, in cardiac surgery and obstetric practice.


2019 ◽  
Vol 30 (2) ◽  
pp. 139-150
Author(s):  
Heather M. Passerini

Health care professionals must understand the impact of blood product transfusions and transfusion therapy procedures to ensure high-quality patient care, positive outcomes, and wise use of resources in blood management programs. Understanding transfusions of blood and blood products is also important because of the number of treatments performed, which affects individual patients and health care system resources. This article reviews research findings to acquaint health care professionals with the most successful protocols for blood, blood product, and coagulation factor transfusions. Damage control resuscitation in bleeding trauma patients, protocols for patients without trauma who are undergoing surgical procedures that place them at risk for excessive bleeding, and protocols for patients with sepsis are addressed. Emerging research continues to help guide mass transfusion treatments (restrictive vs liberal, balanced, and goal-directed treatment). Although available study results provide some guidance, questions remain. Additional research by health care professionals is needed.


Neurosurgery ◽  
2004 ◽  
pp. 487
Author(s):  
Samuel L. Barnett ◽  
Michael Cimo ◽  
Kar???en Matevosyan ◽  
Kevin C. Morrill ◽  
Christopher Madden ◽  
...  

1996 ◽  
Vol 75 (04) ◽  
pp. 590-594 ◽  
Author(s):  
D Massignon ◽  
M Moulsma ◽  
P Bondon ◽  
G Debize ◽  
H Abidi ◽  
...  

SummaryProthrombin-time (PT) sensitivity and specificity to mild clotting factor II, V, VII and X deficiencies have rarely been studied. We therefore carried out a prospective study, in 350 patients, of eight commercial thromboplastins (CTs) in their ability to detect mild clotting factor deficiencies, notably in factor VII. In each patient the factor II, V, VII and X clotting activities and PT performed with each CT were determined. For each CT, PT sensitivity and specificity in detecting factor deficiencies below 0.5 U/ml or below 0.4 U/ml were determined at various PTs, and then Receiver Operator Characteristic curves constructed. At optimum PT threshold level (sensitivity = specificity), exactitude varied from 0.64 to 0.74 (p < 0.01) and from 0.67 to 0.81 (p < 0.0001) in detecting deficiencies below 0.5 and 0.4 U/ml respectively. In conclusion, this study shows the limits of the PT test as performed with 8 CTs in patients with mild clotting factor deficiencies. The impact of such differences in sensitivity and specificity on monitoring certain patients subject to decrease in coagulation factor, and, in particular, of those under low-dose oral anticoagulant, remains to be determined.


2021 ◽  
Vol 10 (2) ◽  
pp. 347
Author(s):  
Barbara Preisler ◽  
Behnaz Pezeshkpoor ◽  
Atanas Banchev ◽  
Ronald Fischer ◽  
Barbara Zieger ◽  
...  

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.


Author(s):  
Housam AL Madani ◽  
Soltan Hassan ◽  
Ghada Ajwa ◽  
Basel Dahlawi

Background: Factor VII deficiency is rare inherited bleeding disorders, have been identified in the Factor VII gene located on chromosome 13 with very few cases reported. Factor VII deficiency was first described by Alexander et al. in 1951.The disorder has also been known as Alexander's disease. It is the rare inherited bleeding disorders’ with an estimated incidence of 1 case per 3,00,000 to 5,00,000 individuals. Objective and method: We did a case report and literature review for deficiency of coagulation factors VII was found in a 4 years patient who had chromosomal aberration 13q deletion syndrome (46, XX, del 13q32-13q33). This loci involved in synthesis or constitution of factor VII. Results: A review of the gene map of chromosome 13 indicated that Factors VII and X are coded on the long arm of chromosome 13, within the deleted region. Conclusion: Congenital Factor VII deficiency is a rare cause of bleeding disorder, which should be suspected in a bleeding child presenting in infancy when platelets and aPTT are normal with abnormal PT. Congenital Factor VII deficiency association with 46, XX, del (13q32– 13q33) syndrome is very rare disorder and further cases should be reported to know the outcome and the risk of complication in such a cases.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hayashi ◽  
I Shimizu ◽  
Y Yoshida ◽  
G Katsuumi ◽  
M Suda ◽  
...  

Abstract   The prevalence of obesity is increasing worldwide. Obese individuals are predisposed to cardio-metabolic disorders. Brown adipose tissue (BAT) is an active metabolic organ abundant with mitochondria, and studies suggest a potential role of BAT in the maintenance of metabolic health in rodents and humans. Metabolic stress causes BAT dysfunction, but the underlying mechanisms are largely unknown. Coagulation factor Xa (FXa) is critically involved in a coagulation cascade, and it is also known to mediate biological effects by the activation of protease-activated receptor (PAR)-signaling. Accumulating evidence shows that PAR1 contributes to tissue remodeling in cardiovascular system. Analyzing deposited microarray data, we found transcripts for coagulation factors including factor VII (F7), factor X (F10), and PAR1 receptor were increased in BAT from obese mice. Here we show a previously unknown role of FXa-PAR signaling in promoting BAT dysfunction and systemic metabolic disorder in a murine dietary obese model. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in tissue factor (TF), coagulation factor VII and FXa in BAT. TF-FVIIa (activated form of FVII)-FXa complex is known to activate PAR1, and we found a significant increase in PAR1 expression in BAT upon metabolic stress. Administration of a FXa inhibitor ameliorated BAT whitening, improved thermogenic response and systemic glucose intolerance upon dietary obesity. Fxa inhibition reduced reactive oxygen species (ROS) level in BAT. In contrast, administration of warfarin did not show any phenotype in BAT. BAT specific TF and PAR1 over-expression model showed significant whitening of this tissue, which was associated with systemic glucose intolerance. We generated BAT specific PAR1 KO mice. BAT-PAR1 KO mice exhibited re-browning of BAT along with reduced ROS level in this tissue. In BAT-PAR1 KO mice, glucose intolerance and thermogenic response under a metabolically stressed condition were ameliorated. In differentiated brown adipocytes, FXa markedly increased mitochondrial ROS and reduced mitochondrial membrane potential. Inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. We also found that plasma FXa level did not increase in obese mice as well as in obese individuals. These results suggest the previously unknown role of coagulation systems in promoting BAT dysfunction, leading to systemic metabolic disorders. Maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes. Funding Acknowledgement Type of funding source: None


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2728-2728
Author(s):  
Karen Matevosyan ◽  
Michael Cimo ◽  
Christopher Madden ◽  
Ravindra Sarode

Abstract OBJECTIVE: To investigate hemostatically important clotting factors in patients with mild to moderate prolongation of PT/INR, who generally receive prophylactic FFP transfusions, especially in neurosurgery, because there is scant data in the literature supporting prophylactic plasma therapy. METHODS: 36 plasma samples from 31 neurosurgical patients with PT/INR 12.5–15.0/1.3–1.5 were separated and frozen within 8 hours of collection; these were tested for coagulation factors II, VII and VIII levels, and PT/INR/PTT values were correlated with the factor levels. Retrospective analysis of all neurosurgery patients for whom FFP was ordered with similar PT/INR values was performed both during 5 months of study period and 5 months post-study period, when changes were implemented in FFP administration guidelines. The PT/INR/PTT values were studied 24 hours following the FFP requests in order to evaluate the effect of plasma infusion. Each group was divided in two subgroups: those who received FFP transfusion within 24 hours of the FFP requests, and those who did not. RESULTS: PT/INR/PTT and coagulation factor levels of the 36 samples are seen in Table 1. PT mean 13.78 INR mean 1.38 PTT mean 29.29 PT median 13.5 INR median 1.3 PTT median 29.5 PT range 10.7–18.6 INR range 0.9–1.9 PTT range 19.3–37.9 FII mean 68% FVII mean 53% FVIII mean 156% FII median 66% FVII median 51% FVIII median 126% FII range 34–107% FVII range 28–124% FVIII range 55–547% There was no correlation between PT/INR with FVII levels (p>0.05). All patients had FVII > 15–25%, level recommended as safe for surgery. FII was also hemostatically normal, whereas mean factor VIII level was elevated, that correlated with shortened PTT in many of these patients. Retrospective analysis revealed that during the study period there were a total of 99 FFP requests (69 patients). Of these 68 requests (46 patients) did and 31 (29 patients) did not receive FFP transfusions within the next 24 hours. Mean number of FFP units transfused was 3.03 (median 2, range 1–7). During the post study period a total of 15 requests (for 14 patients) were received; of these 2 did and 13 did not receive FFP transfusions within the next 24 hours. Mean and median number of FFP was 2. PT/INR/PTT at time of request and 24 hours post transfusion are presented in the Table 2 Study Period (99 FFP requests) Post Study Period (15 FFP requests) Transfused (68) Non-Transfused (31) Transfused (2) Non-Transfused (13) At FFP Request At 24 hrs At FFP Request At 24 hrs At FFP Request At 24 hrs At FFP Request At 24 hrs *PT;†INR;♠PTT 13.42* 12.1 11.9 11.29 14.1 12.8 12.22 11.54 1.3† 1.18 1.16 1.1 1.4 1.3 1.18 1.14 28.9♠ 27.98 27.65 27.43 26.6 27.1 27.4 26.99 CONCLUSION: In patients with a mild prolongation of PT/INR, plasma levels of FII and FVII were hemostatically normal, whereas FVIII levels were increased. After FFP transfusions, PT/INR and PTT values did not change suggesting that plasma therapy in these patients was not warranted. After the study there was a drastic reduction (85%) in FFP orders for prophylactic plasma transfusions.


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