Coagulation Disturbances in Patients with Argininemia

Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

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EXPRESSION IN MAMMALIAN CELLS OF FUSION PROTEINS BETWEEN HUMAN FACTORS IX AND VII

10.1055/s-0038-1643568 ◽

1987 ◽

Author(s):

K L Berkner ◽

S J Busby ◽

J Gambee ◽

A Kumar

Keyword(s):

Fusion Protein ◽

Fusion Proteins ◽

Factor Ix ◽

Biologically Active ◽

Factor Vii ◽

Clotting Factor ◽

Clotting Factors ◽

Mammalian Expression ◽

Plasma Factor ◽

Gla Domain

The vitamin K-dependent plasma proteins demonstrate remarkable similarities in their structures: all have multiple domains in common and extensive homology is observed within many of these domains. In order to investigate the structure-function relationship of these proteins, we have interchanged domains of one protein (factor IX) with that of another (factor VII) and have compared the expression of these fusion proteins with recombinant and native factors IX and VII. Oligonucleotide-directed mutagenesis was used to generate four fusion proteins: factor IX/VII-1, which contains the factor IX leader and gla domain fused to the growth factor and serine protease of factor VII; factor VII/IX-1, a reciprocal fusion protein of factor IX/VII-1; factor IX/VII-2, which contains the factor IX leader adjoined to the mature factor VII protein sequence; and factor VII/IX-2, the reciprocal fusion protein of factor IX/VII-2. The cDNAs encoding all four proteins were cloned into mammalian expression vectors, and to date three of these (factors IX/VII-1, 2 and VII/IX-1) have been transfected into baby hamster kidney (BHK) cells or 293 cells and characterized. Factors IX/VII-1 and VII/IX-1 were both secreted at levels comparable to recombinant factors IX and VII. The factor IX/VII-1 was identical in molecular weight to native or recombinant factor VII (i.e., 53 K). Factor VII/IX-1 was expressed as two proteins with molecular weights around 68 kd, as observed with recombinant factor IX. The factor IX/VII-1 protein has been purified to homogeneity and has been found to possess factor VII biological activity, but at a specific activity approximately 20% that of plasma factor VII. Thus, the gla domain of one clotting factor is capable of directing the activation of another and of generating biologically active protein. In contrast, no activity was observed with the factor IX/VII-2 fusion protein, indicating that there are limits to the interchanges which can generate functional blood clotting factors.

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Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy

Blood ◽

10.1182/blood.v53.3.366.366 ◽

1979 ◽

Vol 53 (3) ◽

pp. 366-374 ◽

Cited By ~ 1

Author(s):

LR Zacharski ◽

R Rosenstein

Keyword(s):

Tissue Factor ◽

Vitamin K ◽

Coagulation Factors ◽

Human Saliva ◽

Factor Vii ◽

Clotting Factor ◽

Activate Factor ◽

Total Protein Content ◽

Factor X ◽

Clotting Factors

Abstract The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.

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Anti-HCV Agent, Ribavirin, Decreases Events of Bleeding in Hemophilia Patients, Possibly by Elevating the Clotting Activity of Factor VII.

Blood ◽

10.1182/blood.v106.11.3214.3214 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3214-3214

Author(s):

Koji Yamamoto ◽

Takashi Honda ◽

Satoshi Suzuki ◽

Hidenori Toyoda ◽

Tadashi Matsushita ◽

...

Keyword(s):

Hepatitis C ◽

Combination Therapy ◽

University Hospital ◽

Factor Vii ◽

Clotting Factor ◽

Hcv Rna ◽

Clotting Factors ◽

Normal Human ◽

Clotting Factor Concentrates ◽

Induced Changes

Abstract Ribavirin has been used in combination with interferon-alpha (IFN-α) to treat chronic hepatitis C. This combination therapy has been reported to be more effective than IFN-α monotherapy for eradicating hepatitis C virus (HCV), including patients with concomitant hemophilia. Eight consecutive hemophilia patients were treated for HCV infection with IFN-α and ribavirin between June 2002 and May 2005 at Nagoya University Hospital as outpatients. Characteristics of patients and responses to anti-HCV treatment Patient Age (yrs) Hemophilia type Severity of hemophilia HIV infection Ribavirin load (mg/day) HCV genotype Eradication of HCV The eradication of HCV was considered positive when the absence of serum HCV RNA was maintained for 24 weeks after treatment was completed. 1 28 A moderate N 800 3a Yes 2 61 A severe N 800 3a Yes 3 50 A severe N 600 --> 400 1b No 4 42 B mild N 800 2a +1b Yes 5 44 A severe N 800 3a Yes 6 52 A mild N 600 2b Yes 7 37 A mild P 800 --> 600 1a No 8 44 B moderate N 800 1a Yes All patients were men with a mean age (SD) of 44.8 (10.0) years. Seven patients had hemophilia A, and 2 had hemophilia B. Hemophilia was severe in 4 patients, moderate in 2 and mild in 3. Four patients had been previously treated with IFN-α-2b alone (Intron A®, Schering Plough, K.K., Osaka, Japan) but HCV had not been eradicated. During this study, all patients were treated with the same 24-week regimen of IFN-α. Oral ribavirin (Rebetol, Schering-Plough, Kenilworth, N.J.) was administered at a dose of 600 mg/day for patients who weighed 60 kg or less and 800 mg/day for those who weighed more than 60 kg during 24 weeks. We observed the reduction of the frequency and dose of infusion with clotting factors as a hemostatic therapy in HCV-positive hemophilia patients who were administered with ribavirin. Figure Figure (Use of clotting factor concentrates 6 months before, during and 6 months after combination therapy with ribavirin and IFN-α. Use of clotting factors is presented as the average use per month.) In order to investigate the mechanism of this prophylactic effect of ribavirin to bleeding in hemophiliacs, we analyzed ribavirin-induced changes in the activity of factor VII in patients’ plasma. The clotting activity of factor VII in plasma has been elevated at 15% on an average in 9 HCV-positive hemophilia patients during treatment with ribavirin (without ribavirin: 86.3±7.6%; with ribavirin: 102.0±10.3%). Furthermore, a significant induction of factor VII mRNA was demonstrated in cultured normal human hepatocytes or HepG2 cells when treated with ribavirin at the therapeutic concentration. These observations indicate that ribavirin can elevate factor VII procoagulant activity in plasma, possibly due to the induction of factor VII in hepatocytes, thus, contributing to decreased events of bleeding in HCV-positive hemophiliacs.

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Extravascular Clotting Factor Activity within Joint Tissues Protects Against Progression of Hemophilic Arthropathy.

Blood ◽

10.1182/blood.v110.11.496.496 ◽

2007 ◽

Vol 110 (11) ◽

pp. 496-496 ◽

Cited By ~ 2

Author(s):

Junjiang Sun ◽

Narine Hakobyan ◽

Leonard A. Valentino ◽

Paul E. Monahan

Keyword(s):

Factor Viii ◽

Coagulation Factor ◽

Joint Capsule ◽

Factor Ix ◽

Clotting Factor ◽

Needle Puncture ◽

Factor Activity ◽

Clotting Factors ◽

Hemophilic Arthropathy ◽

Human Factor Viii

Abstract Hemophilic arthropathy is the major morbidity of congenital factor VIII and IX deficiency. Therapies localized to hemophilic joints could provide adjunctive protection, in addition to that provided by systemic factor replacement. However, the ability of extravascular clotting factors to contribute to hemostatic protection within joint tissue is unknown. We hypothesized that replacing deficient factor VIII or IX within the injured joint capsule of mice with hemophilia A (FVIII −/ −) or hemophilia B (FIX −/ −), respectively, would decrease the progression of synovitis. We developed a bleeding model consisting of a unilateral knee joint capsule needle puncture to induce hemorrhage in hemophilic mice. Pathology of the joint at two weeks after the injury is graded 0 to 10 using a murine hemophilic synovitis grading system (Valentino, Hakobyan. Haemophilia, 2006). Hemostatically normal mice do not develop synovitis following this injury, but > 95% of FIX −/ − mice develop bleeding and synovitis with a mean grade of 3–4 or greater. Coincident with needle puncture, recombinant human coagulation factor doses ranging from 0 to 20 IU/kg body weight of factor IX or 0 to 25 IU/kg of factor VIII were instilled intraarticularly (I.A.). Comparison groups received the same injury and intravenous (I.V.) factor IX or VIII doses of 25 IU/kg to 100 IU/kg (n= 4–7 mice per study group). Joint bleeding phenotype of the two strains of mice was similar. Mice receiving only saline injection at the time of needle puncture developed mean synovitis scores of 5 ±0.5 in the FVIII −/ − mice and 6 ±0.5 in the FIX −/ − mice. Protection by human clotting factor in the mouse coagulation system was incomplete; mice receiving 100 IU/kg I.V. of factor VIII or factor IX developed synovitis scores of 2.6 ± 1.7 and 2.1 ± 0.2, respectively. In contrast, pathology grade of FVIII −/ − mice dosed with 25 IU/kg I.A. was 0.67 ± 0.3 (p = 0.05 for comparison of 25 IU/kg I.A. with 100 IU/kg IV); FIX−/ − mice receiving 20 IU/kg I.A. had synovitis scores of 0.45 ± 0.58 (p < 0.01 for comparison of 25 IU/kg I.A. with 100 IU/kg I.V.). We next ruled out the possibility that I.A. factor was entering the circulation, and via that route resulting in joint protection, either through technical error at the time of injection, or from a depot effect in the joint with late equilibration into the circulation. Additional groups of mice received factor VIII or IX intravenously at 100 IU/kg, or intraarticularly at 4 times the doses used in the hemarthrosis challenge (80 IU/kg FIX or 100 IU/kg FVIII), and factor activity assays were performed at 1, 4, 12, 24, and 48 hours. Expected circulation kinetics were seen following I.V. dosing; no increase in circulating factor VIII or IX activity were seen in the intraarticular dosing groups at any timepoint. In considering the potential immunogenicity of an intraarticular therapy approach for hemophilic joint therapy, factor VIII −/ − mice were treated with three doses of human factor VIII 100 IU/kg at five day intervals either I.V. or I.A. At two weeks after exposure, 5/5 I.V.-treated mice developed inhibitor antibodies with titers ranging 0.8–7.2 BU; 2/5 I.A.-treated mice had detectable low-titer antibodies (1.3 BU), indicating no greater immunogenicity in the I.A. model. Extravascular factor VIII and factor IX can contribute to protection against blood-induced joint deterioration; enhancing local tissue hemostasis with protein or gene therapy may prove a useful adjunct to systemic replacement.

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Coagulation Factor IX concentrate: method of preparation and assessment of potential in vivo thrombogenicity in animal models

Blood ◽

10.1182/blood.v64.6.1220.bloodjournal6461220 ◽

1984 ◽

Vol 64 (6) ◽

pp. 1220-1227

Author(s):

D Menache ◽

HE Behre ◽

CL Orthner ◽

H Nunez ◽

HD Anderson ◽

...

Keyword(s):

Animal Models ◽

Specific Activity ◽

Rabbit Model ◽

Coagulation Factor ◽

Factor Ix ◽

Factor Vii ◽

Factor X ◽

Clotting Factors ◽

Coagulation Factor Ix

Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)- Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX) that is essentially free of prothrombin, factor VII, and factor X. Factor IX specific activity is at least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts of factors II, VII, and X are less than 5 units each per 100 units of factor IX. The concentrate is essentially free of activated clotting factors and contains no added heparin. In the rabbit stasis model, a dose of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the DEAE-Sephadex eluate from which the concentrate was derived. Infusion of 200 factor IX U/kg did not induce DIC in the nonstasis rabbit model, whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in this model. Several factor IX lots were found to have shortened nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic in both animal models. These data indicate that coagulation factor IX concentrate is less thrombogenic than factor IX complex.

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Hepatitis C viral RNA in clotting factor concentrates and the development of hepatitis in recipients

Blood ◽

10.1182/blood.v81.7.1898.bloodjournal8171898 ◽

1993 ◽

Vol 81 (7) ◽

pp. 1898-1902

Author(s):

M Makris ◽

JA Garson ◽

CJ Ring ◽

PW Tuke ◽

RS Tedder ◽

...

Keyword(s):

Hepatitis C ◽

Diagnostic Criteria ◽

Factor Ix ◽

Factor Vii ◽

Clotting Factor ◽

Hcv Rna ◽

Heat Treated ◽

Volunteer Donor ◽

Clotting Factor Concentrates ◽

Donor Plasma

The polymerase chain reaction (PCR) was used to detect hepatitis C (HCV) viral sequences (HCV-RNA) in clotting factor concentrates that had been stored at 4 degrees C for 1 to 16 years. A total of 43 concentrates were tested, comprising 31 batches of factor VIII, 6 of factor IX, 2 of antithrombin III, 3 of FEIBA, and 1 of factor VII. HCV- RNA was detected in 13 of the 43 batches (30.2%). Concentrates that had not undergone viral inactivation during manufacture were significantly more likely to contain detectable HCV-RNA than concentrates that had been virally inactivated (56.3% v 14.5%, P = .006). HCV sequences were more commonly detected in concentrates made from paid donor plasma than in those made from volunteer donor plasma (44% v 11%, P = .041), and more commonly in virally inactivated concentrates with pre-1989 than with post-1989 expiration dates (50% v 0%, P = .004). Of the four batches of heat-treated products that were HCV-RNA positive, at least three transmitted non-A, non-B hepatitis (NANBH). An association between the presence of HCV-RNA in concentrates and the development of NANBH was demonstrated in nine previously untreated patients on prospective follow-up. HCV-RNA was detected in the concentrates administered to the six patients whose alanine aminotransferase (ALT) abnormalities met the diagnostic criteria for NANBH and who later seroconverted for HCV, but it was not detected in the concentrates administered to the three patients whose ALT abnormalities failed to satisfy the diagnostic criteria and who did not seroconvert. We suggest that the use of this PCR technique to monitor clotting factor concentrates derived from pooled blood may potentially contribute to product safety.

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Properties of Recombinant Human Thromboplastin that Determine Sensitivity to Vitamin K-Dependent Coagulation Factors.

Blood ◽

10.1182/blood.v104.11.533.533 ◽

2004 ◽

Vol 104 (11) ◽

pp. 533-533

Author(s):

Stephanie A. Smith ◽

James H. Morrissey

Keyword(s):

Ionic Strength ◽

Vitamin K ◽

Phospholipid Composition ◽

Coagulation Factors ◽

Factor Vii ◽

Clotting Factor ◽

Sensitivity Index ◽

Clotting Factors ◽

Individual Factor ◽

Factor Deficiency

Abstract Patients undergoing oral anticoagulant therapy (OAT) with coumarins have reduced plasma levels of vitamin K-dependent clotting factors. The primary laboratory test for monitoring OAT is the prothrombin time (PT), in which clotting is initiated by tissue factor (TF). Clotting factors that contribute to the PT, and whose levels respond to OAT, are factor VII (FVII), factor X (FX), and prothrombin, although they are not suppressed to the same extent. Thromboplastin reagents (the source of TF activity in PT tests) can vary dramatically in their sensitivities to the effects of OAT. A calibration system, the International Sensitivity Index (ISI), is widely used to correct the PT for variable thromboplastin sensitivity, but discrepant responses by reagents of similar ISI have been reported. We have undertaken studies aimed at understanding which factors control the sensitivity of thromboplastin reagents, with a goal of creating “designer thromboplastins” whose sensitivities to specific clotting factors can be individually tailored. Thromboplastin reagents were prepared by reconstituting recombinant human TF into phospholipid vesicles containing varying amounts of phosphatidylcholine, phosphatidylserine (PS), and phosphatidylethanolamine (PE). Thromboplastins containing low levels of PS and high ionic strength had the highest sensitivity to OAT (i.e., lowest ISI). PE shifted the dose-response such that lower levels of PS were required to obtain the same ISI value. These studies demonstrate that multiple combinations of phospholipid composition and ionic strength can be used to produce reagents of identical ISI. We hypothesized that reagents of identical ISI values but different composition could have very different responses to changes in the levels of individual coagulation factors. Accordingly, thromboplastin reagents of varying composition were evaluated for their responses to deficiencies of FVII, FX and prothrombin. PT tests were performed using pooled normal plasma mixed with individual factor-depleted plasmas to yield 10%, 3%, 1% or 0.3% of the normal level of the specific clotting factor. Responses of thromboplastin reagents to individual factors were compared by plotting the clotting times obtained with these plasmas on log-log scales versus the percent factor level and fitting lines to the data by linear regression. Interestingly, altering the composition of the thromboplastin reagents dramatically and independently altered their sensitivities to individual clotting factors. For example, increasing ionic strength had no impact on the response to FVII, but markedly enhanced the response to prothrombin deficiency. Furthermore, the effect of changes in ionic strength on specific factors levels differed depending upon the phospholipid composition. These studies demonstrate that thromboplastin reagents of dissimilar composition but nearly identical ISI values can have very different sensitivities to deficiencies in FVII, FX, or prothrombin, so reagents of identical ISI do not necessarily respond to the factor deficiencies induced by OAT in an identical fashion. These studies evaluated samples with isolated individual factor deficiency, whereas patients on OAT have combined factor deficiency and therefore have more potential for discrepancy in PT responses between reagents. Controlling the responsiveness of thromboplastin reagents to deficiencies in individual clotting factors may therefore be desirable for monitoring OAT and for the other clinical diagnostic uses to which PT tests are commonly applied.

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Increased Sensitivity of Prothrombin Time Using Recombinant Tissue Thromboplastin Reagents: Implications for Plasma Transfusion.

Blood ◽

10.1182/blood.v106.11.4058.4058 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4058-4058

Author(s):

Adam C. Seegmiller ◽

Ravindra Sarode

Keyword(s):

Prothrombin Time ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Factor Vii ◽

Clotting Factor ◽

Factor Ii ◽

Fresh Frozen ◽

Tissue Homogenates ◽

Tissue Thromboplastin ◽

Clinically Significant

Abstract Acquired coagulopathies are often treated with fresh frozen plasma (FFP) transfusion. Standards for the tranfusion of FFP vary, but are often based on coagulation tests, especially prothrombin time (PT). Previously, the PT test was performed using tissue thromboplastin (TT) reagents derived from human or animal tissue homogenates (hTT). These preparations were fairly crude and varied between manufacturers and lots. Recently, these have been replaced with recombinant TT (rTT) reagents that are more consistent. However, anecdotal reports suggest that rTT is more sensitive to mildly decreased clotting factor levels, leading to longer PTs and increases in FFP transfusion. The purpose of this study is to test the hypothesis that rTT reagents are more sensitive and to determine if thresholds for FFP transfusion should be increased. Fifty plasma samples from patients with prolonged PTs (range 13.0–27.6 seconds; normal 9.2–12.8 seconds) were randomly selected. PTs for each sample were re-measured using rTT (Innovin, Dade-Behring, Liederbach, Germany; ISI=0.91) and hTT (Thromboplastin Reagent, Helena Laboratories, Beaumont, Texas; ISI=2.07) on the same instrument (Start 4 benchtop coagulation analyzer, Diagnostica Stago, Parsippany, New Jersey). These measured PTs are compared in Fig. 1. At the lower end of the PT range (beginning at ~13 seconds), the rTT PTs are shorter, on average, than the hTT PTs. However, the average rTT PT increases at a 1.4 times greater rate than the hTT PT, such that the average PT of the two reagents is equivalent at 16.4 seconds and longer for rTT thereafter. This suggests that the rTT reagent is indeed more sensitive. A similar pattern is seen when factor II and VII levels for each sample are plotted against the corresponding PT (Fig. 2). At high factor levels, the rTT PT is lower, on average, than the hTT PT. However, as factor levels decrease, the rTT PT rises about twice as fast as the hTT PT. The PTs for the two reagents are equivalent at 66% factor II (PT=15.7) and 46% factor VII (PT=17.7). The important thresholds for risk of surgical bleeding are 40% factor II and 25% factor VII. The equivalent PTs in this study are 20.5 (rTT) and 18.1 (hTT) for 40% factor II and 22.3 (rTT) and 19.6 (hTT) for 25% factor VII. These differences are not corrected by converting PTs to the international normalized ratio (INR). Instead, INRs are higher for hTT than rTT, and the degree of difference between the two reagents is greater. The equivalent INRs are 1.90 (rTT) and 2.54 (hTT) for 40% factor II activity, and 2.05 (rTT) and 2.98 (hTT) for 25% factor VII activity. The results of this study confirm that PTs measured using rTT are more sensitive to changes in clotting factor levels than those measured using hTT, especially at clinically significant factor levels. This suggests that thresholds for the transfusion of FFP should be raised at those institutions using rTT. Fig. 1: Comparison of PTs measured Using rTT and hTT Reagents Fig. 1:. Comparison of PTs measured Using rTT and hTT Reagents Fig. 2: Correlation of Prothrombin Time and Factor Levels Fig. 2:. Correlation of Prothrombin Time and Factor Levels

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A new practical technique to reduce allogeneic blood exposure and hospital costs while preserving clotting factors after cardiopulmonary bypass: the Hemobag®

Perfusion ◽

10.1191/0267659105pf831oa ◽

2005 ◽

Vol 20 (6) ◽

pp. 343-349 ◽

Cited By ~ 13

Author(s):

Keith A Samolyk ◽

Scott R Beckmann ◽

Randall C Bissinger

Keyword(s):

Cardiopulmonary Bypass ◽

Bypass Graft ◽

Allogeneic Blood ◽

Factor Vii ◽

Risk Scores ◽

Clotting Factor ◽

Control Group ◽

Fibrinogen Concentration ◽

Heart Team ◽

Clotting Factors

Recent data independently linking allogeneic blood use to increased morbidity and mortality after cardiopulmonary bypass (CPB) warrants the study of new methods to employ unique and familiar technology to reduce allogeneic blood exposure. The Hemobag® allows the open-heart team to concentrate residual CPB circuit contents and return a high volume of autologous clotting factors and blood cells to the patient. Fifty patients from all candidates were arbitrarily selected to receive the Hemobag® (HB) therapy. A retrospective control group of 50 non-Hemobag® (NHB) patients were matched to the HB group patient-by-patient for comparison according to surgeon, type of procedure, age, body surface area (BSA), body weight and CPB time. Many efforts to conserve blood (Cell Saver® and ANH) were employed in both groups. Post-CPB cell washing of circuit contents was additionally employed in the control group. There were no significant differences between the HB and NHB groups in regard to patient morphology, pre-op cell concentrations, distribution of surgeon or procedures (41% valve, 16% valve/coronary artery bypass graft (CABG), balance CABG), pump and ischemic times and Bayes National Risk scores. The average volume returned to the patient from the HB was 8179/198 mL (1 SD). Average processing time was 11 min. The Hemobag®contained an average platelet count of 2309/80 K/mm3, fibrinogen concentration of 4139/171 mg/dl, total protein of 8.09/2.8 gm/dl, albumin of 4.49/1.2 gm/dl and hematocrit of 439/7%. Factor VII, IX and X levels in three HB contents averaged 259% greater than baseline. Substantial reductions were achieved in both allogeneic blood product avoidance and cost to the hospital with use of the HB. Infusion of the Hemobag® concentrate appears to recover safely substantial proteins, clotting factor and cell concentration for all types of cardiac procedures, maintaining the security of a primed circuit.

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Influence of Organ Extracts on Blood Clotting Factors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654405 ◽

1959 ◽

Vol 03 (04) ◽

pp. 491-500 ◽

Cited By ~ 1

Author(s):

P Fantl ◽

H. A Ward

Keyword(s):

Blood Clotting ◽

Factor Ix ◽

Factor Vii ◽

Clotting Factors ◽

Heat Stable ◽

Ether Extraction ◽

The Brain ◽

Blood Clotting Factors

SummaryBrain and lung suspensions incubated with blood or serum produce sera which are deficient in factor IX and factor VII.Suspensions prepared from acetone-dehydrated brain are effective substitutes for free phospholipids in the formation of blood thromboplastin.The fraction which inactivates the clotting factors is connected with a readily sedimentable portion of the brain suspension.It is heat stable, and destroyed by ethanol-ether extraction.The extracted lipid is inactive.

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