In vitro effects of a kaolin-coated hemostatic dressing on anticoagulated blood.

BACKGROUND: The use of kaolin-coated dressings has become common and have efficacy in normal patients, but their increased use will inevitably include use on bleeding patients taking anticoagulants. We hypothesize that kaolin coating material (KCM) will improve clotting regardless of anticoagulation medication. METHODS: A prospective study was performed on blood from patients who were on a vitamin K antagonist (VKA), unfractionated heparin (UH), an antiplatelet (AP) agent, a Xa inhibitor (Xa), or a direct thrombin inhibitor (DTI). None were on more than one type of anticoagulation medication. Viscoelastic testing was performed with and without KCM. All p values were adjusted for multiple comparisons. RESULTS: The addition of KCM significantly decreased the time for initial clot formation (CT) in all groups. The mean CT for controls was decreased from 692 to 190.8 s (p < 0.0001). KCM decreased the initial clot formation time by about 1.5 times in those on DTI (p = 0.043) and 2.5 times in those taking AP medication (p < 0.001). The most profound effect was seen in those on UH (no KCM 1,602 s vs. KCM 440 s; p < 0.001), VKA (no KCM 1,152 s vs. 232 s; p < 0.01), and Xa (no KCM 1,342 s vs. 287 s; p < 0.001). Analysis of other clot formation parameters revealed that KCM significantly improved the clot formation kinetics (CFT) only in patients taking Xa (p = 0.03). KCM improved maximum clot strength in patients on Xa inhibitors (p = 0.05). Patients on UH had a larger effect size with an increase in clot strength from 24.35 mm to 43.35 mm whereas those on Xa had an increase of 38.7 mm to 49.85 mm. CONCLUSION: In this in vitro analysis, the addition of KCM to the blood of patients taking any of these anticoagulation medications significantly improved the time to initial clot formation, indicating that kaolin-based hemostatic dressings will be effective in initiating clot formation in patients on anticoagulants. LEVEL OF EVIDENCE: Therapeutic, level IV.

Impact of experimental hypercalcemia on routine haemostasis testing.

BACKGROUND: The blood to anticoagulant ratio is standardized according to the physiological calcium concentration in blood samples conventionally used for hemostasis testing. Specifically, one fixed volume of 0.109 mmol/L sodium citrate is added to 9 volumes of blood. Since little is known about the impact of hypercalcemia on the calcium-binding capacity of citrate, this study was planned to investigate the effect of experimental hypercalcemia on routine hemostasis testing. METHODS: Fifteen pooled citrated plasmas with matching lithium-heparin pooled plasma from patients with different values of prothrombin time (PT) were divided in three aliquots of 0.6mL each. The first paired aliquots of both citrate and lithium-heparin plasma were supplemented with 60µL of saline, the second paired aliquots with 30µL of saline and 30µL of calcium chloride and the third paired aliquots with 60µL of calcium chloride. Total and ionized calcium was measured in all aliquots of citrate and lithium-heparin plasma, whereas PT, activated partial thromboplastin time (APTT) and fibrinogen were measured in citrate plasma aliquots. RESULTS: Total calcium concentration gradually increased in both lithium-heparin and citrate plasma aliquots 2 and 3 compared to baseline aliquot 1. The concentration of ionized calcium also gradually increased in lithium-heparin plasma aliquots 2 and 3, whereas it remained immeasurable (i.e., <0.10 mmol/L) in all citrate plasma aliquots. No significant differences were observed for values of PT, APTT and fibrinogen in citrate plasma aliquots 2 and 3 compared to the baseline aliquot 1, with a mean bias was always comprised within the desirable quality specifications derived from biological variability data. CONCLUSION: Hypercalcemia, up to severe hypercalcemia does not generate significant bias in results of first-line coagulations tests, so that hypothetical consideration of adjusting citrate-blood ratio is unjustified in hypercalcemic patients.

Direct oral anticoagulants and heparins: laboratory values and pitfalls in 'bridging therapy'.

Objectives: The three direct oral anticoagulants (DOACs) dabigatran, apixaban and rivaroxaban are now widely used in clinical practice. For patients requiring perioperative interruption of DOACs, heparin bridging is still under discussion. Here we show, for the first time, the influence of concomitantly used DOACs and heparins on laboratory assays. Methods: For spiking experiments, 10 healthy donors and nine patients treated with DOACs were investigated. The measurement of DOACs and heparins was performed with routine methods on the ACL TOP [HEMOCLOT ® direct thrombin inhibitor (CoaChrom Diagnostica, Austria), COAMATIC ® Heparin (Chromogenix, USA) calibrated with rivaroxaban, apixaban, unfractionated heparin (UFH) and low molecular weight heparin (LMWH), additionally PT reagent RecombiPlasTin 2G and aPTT reagent SynthASil (Instrumentation Laboratory, Germany)] and the DOACs were additionally quantified with liquid chromatography-mass spectrometry. A linear regression model has been used to estimate the effect of DOAC prestimulation. Results: No influence of dabigatran could be demonstrated in the anti-Xa testing methods for LMWH, UFH, rivaroxaban or apixaban. All FXa-inhibiting drugs affected all the anti-Xa testing methods in their own specific ways. Compared with heparin alone, measurement of heparins in samples with a basic concentration of DOACs (200 ng/ml) displays a more dramatic increase. Samples of patients with therapeutic intake of DOACs spiked with UFH and LMWH showed the expected pharmacokinetic profiles, but increased pharmacodynamic effects. Conclusions: Direct thrombin and FXa inhibitors exhibit distinct effects on assay results when used concomitantly with heparins. These interactions must be considered in the interpretation of assay results during bridging therapy.

Thromboprophylaxis With Heparin During Orthotopic Liver Transplantation: Comparison of Hepcon HMS Plus and Anti-Xa Assays for Low-Range Heparin.

OBJECTIVES: The purpose of this study was to compare the agreement between two heparin assays, Hepcon HMS plus/Kaolin-ACT and Anti-Xa, and their predictive power in detecting circulating heparin levels post-reperfusion of the liver graft when compared with thromboelastogram (TEG) r time ratio in patients undergoing orthotopic liver transplantation (OLT). DESIGN: Prospective, observational cohort study design. SETTING: Single center, university hospital. PARTICIPANTS: Thirty-eight consecutive adults who had undergone liver transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Paired arterial blood samples were collected before surgical incision, 5 minutes after administration of an average dose of 2,054±771 units of intravenous unfractionated heparin before caval cross-clamping, 5 minutes after portal reperfusion, 5 minutes after hepatic artery reperfusion, and 1 hour after hepatic artery reperfusion. The observations that heparin assay measurements were within the predetermined limits of agreement, strongly suggested the two heparin assays (Hepcon HMS plus and Anti-Xa assay) are interchangeable during prophylactic heparin dose therapy during OLT. Post-reperfusion, receiver operating characteristic curve analysis revealed high accuracy in measuring circulating heparin levels with both Anti-Xa and Hepcon HMS assays when compared with the TEG r time ratio assay. CONCLUSIONS: The point-of-care Hepcon HMS plus/Kaolin-ACT (activated clotting time) assay appeared to be a reliable alternative to the more expensive and laboratory-required Anti-Xa assay in monitoring the response to intravenous heparin in patients undergoing OLT.

Reinfusate Heparin Concentrations Produced by Two Autotransfusion Systems.

OBJECTIVES: Cell saver reinfusate ideally should contain low, clinically insignificant heparin concentrations. The American Association of Blood Banks has defined the clinically insignificant threshold as 0.5 IU/mL. Furthermore, there is uncertainty about the meaning of cell saver "heparin elimination rates." These concerns prompted the authors' independent investigation of reinfusate heparin concentrations of devices used in their institution. It was hypothesized that cell saver reinfusates contain clinically insignificant heparin concentrations. DESIGN: Two prospective, pragmatic, sequential, observational, single-center studies. SETTING: University teaching hospital. PARTICIPANTS: A total of 32 and 31 patients for on-pump cardiac surgery were enrolled in the Sorin (Dideco) Electa and Sorin Xtra studies, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postcardiac surgery reinfusate heparin concentrations were measured using a modified anti-Xa chromogenic assay. Heparin concentrations above 0.5 IU/mL were present in 56% (95% confidence interval, 35% to 68%) of Sorin Xtra reinfusates. Heparin concentrations in the Sorin (Dideco) Electa reinfusates were lower than recommended in 29 of 32 reinfusates. Only 3 of 32 Sorin (Dideco) Electa reinfusates (9.4%; 95% confidence interval 3.2% to 24%) exhibited heparin concentrations exceeding 0.5 IU/mL. CONCLUSIONS: Sorin (Dideco) Electa reinfusates contained heparin concentrations below the American Association of Blood Banks recommended threshold in 90.6% of cases, while Sorin Xtra reinfusate heparin concentrations exceeded this recommendation in 56% of cases. Measurement of cell saver reinfusate heparin concentrations necessitates the use of a modified chromogenic assay. Studies explicitly should confirm that such a modification was indeed used. Periodic quality control of reinfusate composition is recommended.

Etiology of senile osteoporosis: a hypothesis.

UNLABELLED: Osteoporosis is a major health problem characterized by compromised bone strength predisposing patients to an increased risk of fracture. It may cause morbidity and mortality in elderly men and women. The etiologic factors that lead to senile osteoporosis still are unclear. Based on the available experimental and clinical evidence, we update our earlier proposal that zinc deficiency plays a role in the pathogenesis of senile osteoporosis. However, the mechanism of zinc deficiency in osteoporosis remains unclear. Zinc deficiency may lead to the increase of endogenous heparin probably causing degranulation of mast cells and release of endogenous heparin, and an increase in the bone-resorbing effect of prostaglandin E2. Endogenous heparin and prostaglandin E2 are probably cofactors of parathyroid hormone and may have a role in the pathogenesis of senile osteoporosis enhancing the action of parathyroid hormone. Therefore, zinc replacement by dietary zinc supplementation might be valuable to prevent or treat senile osteoporosis. Additional studies are necessary for the evaluation of the possible role of zinc in the etiology of senile osteoporosis. LEVEL OF EVIDENCE: Level V (expert opinion). See the Guidelines for Authors for a complete description of the levels of evidence.

[Effect of the medicinal leech salivary gland secretion on the state of rat subcutaneous mast cells].

It is firstly showed that the medicinal leech salivary gland secretion (SGS) as a polycomponent system of proteins and low-molecular weight substances, activates rat subcutaneous mast cells in vitro prompting a decrease in the heparin saturation index and increasing some characteristic mast cells morphometric parameters. The same mast cell changes were detected by analysis of some specimens of subcutaneous cellular tissue in the point of skin injured by the leech bite. It is shown that these changes are saved during 3 days. The mechanical injury of rat skin does not effect the mast cells activation. Activation of mast cells by SGS is extended to the distant subcutaneous mast cells. It is expressed in sharp decreasing of heparin saturation index although not statistically positive. The secondary leeching on these distant points provokes reduction of mast cells activation and some decrease of post-leeching blood heparin content: 0.154 +/- 0.03 units/ml (n = 10) as compared with post-leeching blood heparin contents analysed from the wound after the primary leeching (0.160 +/- 0.03 units/ml, n = 10). Proceeding from these findings, participation of heparin secreted from activated mast cells in the support of post-leeching bleeding is suggested, the phenomenon which provides unloading of capillary pool by application of medicinal leeches for treatment many diseases.

Volume of RBCs, 24- and 48-hour posttransfusion survivals, and the lifespan of (51)Cr and biotin-X-N-hydroxysuccinimide (NHS)-labeled autologous baboon RBCs: effect of the anticoagulant and blood pH on (51)Cr and biotin-X-NHS elution in vivo.

BACKGROUND: The RBC injury that occurs during collection of the first few milliliters of blood into the pH 5.0 ACD (NIH, Formula A) is referred to as the lesion of collection. The RBC injury was evaluated by labeling the ACD RBCs with (51)Cr and measuring the 24-hour posttransfusion survival. The effect of the acidification of ACD blood on the in vivo elution of (51)Cr from the RBC has not been reported. STUDY DESIGN AND METHODS: Baboon blood was collected in heparin and in ACD and CP2D at different ratios of blood to anticoagulant. ACD blood with a pH of 5.7 to 6.9 was labeled with (51)Cr. Heparinized blood with a pH of 7.4 was labeled with biotin-X-N-hydroxysuccinimide (NHS). ACD blood with a pH of 5.9 was labeled with both (51)Cr and biotin-X-NHS. The RBC volumes, 24- and 48-hour posttransfusion survivals, and lifespans (T50) were measured. RESULTS: The RBC volume of ACD blood with a pH ranging from 5.7 to 6.9 was not affected by (51)Cr labeling. (51)Cr-labeled ACD blood with a pH of 6.9 had an RBC volume that was significantly greater than that seen in heparinized blood with a pH of 7.4 labeled with biotin-X-NHS. In vivo elution of (51)Cr from the RBCs prepared from the ACD blood with a pH of 5.7 to 6.9 and in vivo elution of biotin-X-NHS from RBCs prepared from ACD blood with a pH of 5.9 were associated with reductions in 24- and 48-hour posttransfusion survivals and T50. CONCLUSIONS: The anticoagulant and the pH of the medium in which the RBCs were labeled with (51)Cr or biotin-X-NHS affected in vivo elution of the label from the RBCs and may reduce posttransfusion survival values.

Centrifugation of salvaged pump blood is useful in reducing the amount of heparin re-infused into the patient.

Conservation of blood and blood products are of major concern in clinical practice today. All blood salvaged from the extracorporeal circuit at the end of cardiopulmonary bypass should be returned to the patient. We propose the use of a simple and inexpensive centrifuge machine to reduce the amount of heparin from the residual pump blood re-infused to the patient. At the same time, the re-infused blood is concentrated. Sixteen patients were prospectively included in this study. The residual pump blood was collected from the bypass circuit and spun at 4,000 rpm for 7 min on the Jouan GR 4.22 machine. The clear upper supernatant was discarded and the remaining concentrated red cells re-infused back to the patient. The heparin concentration and full blood counts of both layers were measured. We found that this method was useful in removing excessive heparin and avoiding the need for additional protamine.

The monitoring of heparin administration by screening tests in experimental dogs.

The objective of this study was to investigate the relationship between different screening tests of haemostasis and amidolytic plasma activities of unfractionated (standard) heparin in dogs. Different doses of intravenous (i.v.) [25, 50 or 100 IU Kg(-1)bodyweight (BW)] and subcutaneous (s.c.) heparin (250, 500 and 750 IU kg(-1)) were given to groups each of five clinically healthy adult beagles. Measurements of heparin activity with a factor Xa-dependent chromogenic substrate, activated partial thromboplastin time (APTT) (two different reagents), thrombin time (TT, two different thrombin activities in the reagent: 3 and 6 IU ml(-1)) and the reaction time of the resonance thrombogram (RTG -r) with two different measuring devices were performed at different times. The relationship between ratio values (actual/baseline values) of the coagulation tests and heparin activity was analysed based on regression analysis and correlation coefficient. The greatest alterations were seen for the TT([3 IU ml(-1)])and the RTG -r which were near or exceeded the upper limit of measuring range, if 25 IU kg(-1)BW heparin were given i.v. at heparin plasma levels of 0.54 +/- 0.13 IU ml(-1). These results show, that only APTT and TT measured with high thrombin activity assay appear suitable for guiding high dose heparin therapy in dogs. Averaged alterations of APTT ratio in canine plasma were less than those observed in people for similar plasma heparin levels, indicating that the guideline extrapolated from people for monitoring high dose heparin therapy using APTT may not be valid for use in dogs. After coagulation times had been converted into ratio values, based on regression analysis and Wilcoxon's test, differences of heparin sensitivity were found not only for TT measured with different thrombin activities but also for different APTT reagents (P < 0.001). The correlation between amidylotic antifactor Xa activity and ratio of coagulation times was only moderate and found to be lower for RTG -r (instrument 1: r(s)= 0.711; instrument 2: r(s)= 0.573) than for the other coagulation tests (r(s)= 0.822 to r(s)= 0.890). This indicates a considerable variability of the ratio values of the screening tests at defined heparin plasma activities. These results show, that blood coagulation tests in general are little or unsuitable for heparin antifactor-Xa activity control.

Alternative methods for anticoagulation monitoring in pediatric patients with applicability to a patient with severe hemophilia A and circulating inhibitor.

Anticoagulation monitoring in pediatric patients can be problematic because of the immaturity of the coagulation system in this population. In addition, the hemodilution required to place a small patient on bypass can interfere with standard monitoring methods. In this institution, the Hemochron Jr. ACT (activated clotting time)+ assay has been the standard of care for anticoagulation monitoring since 1997. This assay, with a target ACT of 400 s for initiating bypass, was compared to both the Medtronic HMS system (N = 7) and the Hemochron HiTT assay (N = 6) in pediatric patients. All three assays were then employed to monitor a pediatric Hemophilia A patient (Factor VIII <1%) with high inhibitor titer. Both the HiTT clotting time and the HMS heparin level showed statistically significant correlation to the ACT+ (HiTT, N = 24, r = 0.761; HMS, N = 31, r = 0.818). An HMS target heparin level of 1.5 mg/kg and a HiTT target clotting time of 180 s were found to be clinically equivalent to the 400-s ACT+ as indicators of the need for additional heparin. When a 7-year-old male with severe hemophilia A and high inhibitor titer required tricuspid valve replacement, all three assays were used to ensure appropriate anticoagulation management. During bypass, this patient's ACT+ remained out of range (>1005 s). The HiTT was maintained at >180 s and the HMS heparin level at >1.5 mg/kg. Heparin was administered when any single parameter was below the cutoff value. The use of the combination of three distinct monitoring assays for this patient allowed the surgical team an added level of confidence that appropriate anticoagulation had been maintained.

Effects of unprocessed and processed cardiopulmonary bypass blood retransfused into patients after cardiac surgery.

BACKGROUND: The aim of this prospective study was to compare the effect of autologous unprocessed to processed residual cardiopulmonary bypass blood (CPB) on patients' laboratory and clinical parameters and outcome. METHODS: 20 patients undergoing elective coronary artery bypass surgery were randomized to receive either unprocessed CPB blood (control group) or processed CPB blood employing the Continuous AutoTransfusion System (CATS; Fresenius, Bad Homburg, Germany). We have shown that this method eliminated >93% of activated mediators. Serial laboratory parameters including complement activation, coagulation factors and the stimulation of IL-6 and IL-8 were compared with clinical side effects and patients' outcome. RESULTS: Compared to control patients, retransfusion of unprocessed CBP blood significantly increased heparin, free plasma hemoglobin and D-Dimers. Postoperatively, three patients in the control group and two patients in the CATS group required prolonged mechanical ventilation or developed infections associated respectively with elevated C3a (desArg) or IL-6 concentration. CONCLUSIONS: CATS-processing of CPB blood provided a high-quality red blood cell concentrate, resulting in a reduced load of retransfused activated mediators.

[Heparin-induced coagulation disturbance from mechanical autotransfusion]. / Heparininduzierte Gerinnungsstörung durch maschinelle Autotransfusion.

UNLABELLED: Disorders in blood coagulation during the use of autotransfusion have been reported in recent literature. We wondered whether or not heparine, remaining in the prepared sample of retransfusion blood might be responsible for these disturbances. METHODS: Therefore we created a setting in which heparine was added to animal blood in order to imitate clinical situations during the use of the CELL SAVER. RESULTS: According to our results the blood shows no irregular heparine load as long as the machine is used following the operating instructions. But if the volume of rinsing liquid is decreased or the pumpflow is increased, the heparine load is increased enormously (Table 1). CONCLUSIONS: If the CELL SAVER is used with reduced volume of rinsing liquid or higher velocity of the pump, the coagulation status of the patient has to be monitored meticously.

Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis.

In a previous study we observed extensive clotting and fibrinolysis in blood from the thoracic cavities during cardiopulmonary bypass. We hypothesized that retransfusion of this suctioned blood could impair hemostasis. In this prospective clinical study we investigated the effect of suctioned blood retransfusion on systemic blood activation and on postoperative hemostasis. During coronary artery bypass grafting in 40 patients, suctioned blood was collected separately. It then was retransfused to the patient at the end of the operation (n = 19), or it was retained (n = 21). During the study, 12 consecutive patients, randomized in two groups of 6, were analyzed for biochemical parameters indicating blood activation and clotting. The immediate and significant increase in circulating concentrations of thrombin-antithrombin III complex, tissue-type plasminogen activator, fibrin degradation products, and free plasma hemoglobin demonstrated the effect of suctioned blood retransfusion. Moreover, the increased concentrations of thrombin-antithrombin III complex and fibrin degradation products indicated renewed systemic clotting and fibrinolysis as a direct result of the retransfusion of suctioned blood. Concentrations of all indicators mentioned remained significantly lower in the retainment group. The clinical data showed that retainment of suctioned blood resulted in significantly decreased postoperative blood loss (822 mL in the retransfusion group versus 611 mL in the retainment group; p < 0.05) and similar or even reduced consumption of blood products (513 versus 414 mL red blood cell concentrate and 384 versus 150 mL single-donor plasma; both not significant). We conclude that retransfusion of highly activated suctioned blood during cardiopulmonary bypass exacerbates wound bleeding.

In vitro model to test the thrombogenicity of coronary stents.

Thrombotic occlusion is a major complication limiting the application of stents in coronary arteries. In an in vitro model we investigated the thrombogenicity of different stent materials and several medical regimens to prevent thrombotic occlusion. Experiments were conducted in a closed system of silicon tubing with circulating citrated platelet rich plasma of healthy volunteers (n = 7) and of patients (n = 7 for each condition). Patients were either treated with phenprocoumon or with high or low dose heparin in combination with aspirin alone (100 mg) or aspirin (990 mg) plus dipyridamole (225 mg). After placement of tantalum wire stents into the system platelet aggregates were visible after 13.5 +/- 3.0 min, and occlusion occurred after 15.0 +/- 3.5 min. Similarly, with implanted stainless steel stents aggregation was seen after 13.0 +/- 3.5 min and thrombosis occurred after 14.5 +/- 3.5 min (p < 0.001 vs control without stent). Microscopic examination revealed combined platelet fibrin thrombi occluding the lumen. Platelet components predominately covered stent wires, particularly at crossing points. In all experiments high-dose heparin prevented platelet aggregate formation and stent occlusion independently of additional aspirin or aspirin plus dipyridamole; perfusion time > 60 min (p < 0.001 vs no heparin). Low-dose heparin could not prevent clotting. With aspirin alone aggregates were visible after 16.0 +/- 4.0 min and clotting occurred after 23.0 +/- 5.0 min. In combination with dipyridamole aggregates were visible after 15.5 +/- 5.0 min and clotting after 21.0 +/- 4.0 min (NS vs aspirin alone). Phenprocoumon prevented platelet aggregate formation and stent occlusion; perfusion time > 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

[Is the activated partial thromboplastin time suitable for monitoring of thrombosis therapy with high-dose standard heparin?]. / Ist die aktivierte partielle Thromboplastinzeit (aPTT, PTT) zur Uberwachung der Thrombose-therapie mit hochdosiertem Standard-Heparin geeignet?

The activated partial thromboplastin time (aPTT, PTT) is widely used to monitor therapeutic anticoagulation with standard heparin. However, it has been known for some time that PTT reagents obtained from various manufacturers display different sensitivities to heparin--a fact which often is not taken into account. The study deals with the question whether the sensitivity of the PTT to heparin is additionally influenced by the decrease in the vitamin K-dependent coagulation factors such as occurs after starting oral anticoagulation (OAC). In in-vitro studies the reaction of the PTT was observed after addition of different amounts of heparin to normal plasma, to plasma taken after the start of OAC and during stable OAC. The results show that the PTT tends to be more sensitive to heparin as soon as oral anticoagulation is initiated. This phenomenon already occurs at an early stage of anticoagulant intake where only factor VII is markedly reduced but prothrombin concentration is still in an almost normal range and therefore a clinically sufficient effect of OAC is not to be expected. Identical results are obtained with plasma samples of heparin treated patients before and after the start of OAC; in addition, a scattering of the PTTs is obvious. This leads to overestimation of heparin concentrations and a consequent reduction of dosage at an early, still insufficient stage of OAC. In contrast, the thrombin time shows--independently of OAC--a good correlation to heparin concentrations. Therefore the thrombin time is more appropriate to monitor heparin therapy in the phase when oral anticoagulation is started.

Clinical significance of heparin in the residual pump oxygenator blood, reinfused postoperatively after cardiopulmonary bypass.

Postcardiopulmonary bypass (CPB) heparin levels and thrombin time were measured in 20 patients following routine open cardiac operations. There was a statistically significant increase in heparin concentration and thrombin time ratio on completion of transfusion of the residual pump oxygenator blood. An hour after the end of the transfusion there was no statistically significant difference in the heparin concentration and thrombin time ratio compared to values before and immediately after transfusion. We also observed a significant decrease in the chest drainage over a period of four hours which was unrelated to plasma heparin level. Measurements of thrombin time in the post bypass period closely follow plasma heparin levels. If postoperative bleeding arose it was due to inadequate surgical haemostasis or coagulation defect other than residual heparinization. Thus this confirms further that heparin is not the sole aetiological factor in postoperative bleeding post-CPB.

Heparin removal in three intraoperative blood savers in cardiac surgery.

The aim of the study was to compare the residual heparin in the composition of autologous blood retransfusion units harvested during cardiac surgery under extra-corporeal circulation with three different intraoperative autologous blood savers. In this institutionally approved study, thirty patients undergoing CABG were randomly assigned to three groups according to the intraoperative blood saver used during the procedure: {HAEMONETICS Cell Saver IV (n=10)--DIDECO/SHILEY STAT (n=11)--BRAT 250 (n=9)}. Anaesthesia and conduct of bypass were identical for all patients. The initial heparin dose was 300IU-kg -1 and was supplemented to maintain an activated coagulation time over 480s. The harvested blood was processed according to the procedure defined by each equipment manufacturer. The biological study was performed on the first blood sediments sampled before administering protamine to the patient. Blood cell count, residual heparinemia assessed by its anti-Xa activity using an amidolytic method {STACHROM HEPARIN--DIAGNOSTICA STAGO}, and weight of the blood sediment proteins were determined. Demographic data did not differ between groups. Despite a slight but significant difference between groups, the three devices provided virtual elimination of heparin. The total protein content was significantly higher in the BRAT 250 group. There was a highly significant positive correlation between the anti-Xa activity and total protein content. Haematologic data were within clinically acceptable ranges.