Anticoagulation,bleeding, and clotting at donor plasmapheresis

This article is based on a question of a colleague from North America how coagulation could be triggered between a donor's arm and a fistula needle during plasma donation (synonymous with donor plasmapheresis). The technique of venipuncture and citrate anticoagulation are described. Uncommon and rare problems such as prolonged bleeding, scarring, and thrombosis in plasma donors are discussed. If venous puncture and citrate: blood flow ratio at 1:16 are correctly performed, however, there will be no anticoagulation abnormalities due to plasma donation.     

A novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration

OBJECTIVE: Validation of a novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration (CVVHDF). DESIGN AND SETTING: Prospective cohort trial in medicosurgical intensive care units of two university-affiliated teaching institutions. PATIENTS: Participants were patients at high risk for bleeding, with renal failure requiring CVVHDF without heparin. Fourteen patients completed the study. INTERVENTION: A convection-based citrate anticoagulation CVVHDF regimen using an isotonic replacement fluid containing citrate administered in predilution. A neutralizing solution of calcium chloride and magnesium sulfate was infused at the end of the circuit. Blood flow rate was set and kept at 125 ml/min, and the flow rate of the replacement fluid was initiated at 1250 ml/h and adjusted thereafter according to the monitoring of blood activated coagulation time (ACT), with a target between 180 to 220 s. MEASUREMENTS AND RESULTS: The average filter time-life was 44 h. Thrombosis of the proximal portion of the circuit (which was not anticoagulated) was the main reason for technique failure. A mean urea clearance of 21 ml/min was obtained. Electrolytes and acid-base balance were both well maintained. Six percent (16/287) of Ca(i) readings less than 0.3 mmol/l were associated with very high ACT levels (>300 s). CONCLUSIONS: This regimen is shown to be safe, efficacious, and convenient. Citrate anticoagulation should be monitored using postfilter ACT and/or ionized calcium with respective targets of 200-250 s or 0.3-0.4 mmol/l.     

简化局部枸橼酸抗凝在连续性静-静脉血液滤过中的应用

目的 探讨简化局部枸橼酸抗凝(RCA)在连续性静-静脉血液滤过(CVVH)中应用的安全性与有效性.方法 14例患者用简化RCA方法行CVVH治疗,将枸橼酸钠置换液以2 000 ml/h或3 000 ml/h的速度前稀释输入,10%葡萄糖酸钙和25%硫酸镁从外周静脉泵入或滤器静脉端输入;分别于治疗前及治疗后4、8、12 h测定患者血清电解质、血气分析、凝血功能,并观察患者病情变化,测定治疗后滤器容积.结果 14例患者共进行CVVH治疗34例次,治疗时间4～36 h,平均(16.0±7.5)h;30例次未更换滤器完成治疗,治疗后滤器容积(97.19±2.75)ml,均大于原有容积的80%;滤器使用寿命平均(14.79±5.98)h.治疗12 h时患者滤器动脉端采血检测凝血酶原时间(PT)较治疗前明显缩短[(12.2±1.2)s比(14.0±3.3)s],且滤器动脉端血浆总钙明显升高[(2.46±0.30)mmol/L比(2.07±0.36)mmol/L,均P<0.05];而滤器动脉端采血检测活化部分凝血活酶时间(APTT)、凝血酶时间(TT)及Ca2+、Mg2+浓度和pH值、剩余碱(BE)均无明显变化.1例低氧血症患者因严重并发症停止治疗;均未出现高钠血症、碱中毒、出血并发症.结论 将拘橼酸钠加人置换液中的简化RCA方法可以安全用于置换液速度>2 000 ml/h的CVVH;并可避免RCA导致的高钠血症、碱中毒等并发症.     

Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: A community-based cohort study

Background

The use of mouse models for the study of thrombotic disorders has gained increasing importance. Methods for measurement of coagulation activation in mice are, however, scarce. The primary aim of this study was to develop a specific mouse thrombin-antithrombin (TAT) ELISA for measurement of coagulation activation and to compare it with two commercially available assays for human TAT complexes. In addition, we aimed to improve methods for mouse plasma anticoagulation and preparation.

Methods and results

First, for the measurement of TAT-complexes in plasma a mouse specific TAT-ELISA was developed using rabbit polyclonal antibodies raised against mouse thrombin and rat antithrombin, respectively. This ELISA detected an increase in TAT levels in a mouse model of endotoxemia. Two commercial human TAT ELISAs appeared to be less specific for mouse thrombin-rat antithrombin complexes. Second, to prevent clotting of mouse blood sodium citrate was either mixed with blood during collection in a syringe or was injected intravenously immediately prior to blood collection. Intravenous sodium citrate completely inhibited blood coagulation resulting in plasma with consistently low TAT levels. Sodium citrate mixed with blood during collection resulted in increased TAT levels in 4 out of 16 plasma samples. Third, heparinase was added to plasma samples after in vivo injection of different heparin doses to test its neutralizing effect. Heparinase neutralized up to a 20 U of heparin/mouse and resulted in accurate APTT and factor VIII determinations.

Conclusion

These procedures and reagents for plasma preparation and coagulation testing will improve studies on thrombotic disorders in mice.     

Total-to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients

ABSTRACT: INTRODUCTION: Regional citrate anticoagulation is safe, feasible and increasingly used in critically ill patients on continuous renal replacement therapy (CRRT). However, in patients with hepatic or multi-organ dysfunction, citrate accumulation may lead to an imbalance of calcium homeostasis. The study aimed at evaluating the incidence and prognostic relevance of an increased total to ionized calcium ratio (T/I Ca2+ ratio) and its association to hepatic dysfunction. METHODS: We performed a prospective observational study on n = 208 critically ill patients with acute kidney injury (AKI) and necessity for CRRT with regional citrate anticoagulation (CRRT-citrate) between September 2009 and September 2011. Critical illness was estimated by Simplified Acute Physiology Score II; hepatic function was measured with indocyanine green plasma disappearance rate. After achieving a steady state of calcium homeostasis patients were classified into tertiles according to the T/I Ca2+ ratio (<2.0 versus 2.0 - 2.39 versus ≥2.4). RESULTS: The T/I Ca2+ ratio was determined as an independent predictor for 28-day mortality in critically ill patients with AKI on CRRT-citrate confirmed by receiver operating characteristics and multivariate analysis (Area under the curve 0.94 ± 0.02; p<0.001). A T/I Ca2+ ratio ≥2.4 independently predicted a 33.5-fold (p<0.001) increase in 28-day mortality-rate. There was a significant correlation between the T/I Ca2+ ratio and the hepatic clearance (p<0.001) and the severity of critical illness (p<0.001). The efficacy and safety of citrate anticoagulation, determined by blood urea nitrogen, mean filter patency and bleeding episodes, were not significantly different between the tertiles. CONCLUSIONS: In patients on CRRT-citrate T/I Ca2+ ratio is closely related to the clinical outcome and emerged as an independent predictor of 28-day mortality. Larger studies are required to define the cut-off and predictive value for the T/I Ca2+ ratio. This ratio is associated with hepatic and/or multi-organ dysfunction and therefore an important therapeutic target.     

Emergency medicine misconceptions: Utility of routine coagulation panels in the emergency department setting

BackgroundCoagulation panels are ordered for a variety of conditions in the emergency department (ED).ObjectiveThis narrative review evaluates specific conditions for which a coagulation panel is commonly ordered but has limited utility in medical decision-making.DiscussionCoagulation panels consist of partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR). These tests evaluate the coagulation pathway which leads to formation of a fibrin clot. The coagulation panel can monitor warfarin and heparin therapy, evaluate for vitamin K deficiency, evaluate for malnutrition or severe systemic disease, and assess hemostatic function in the setting of bleeding. The utility of coagulation testing in chest pain evaluation, routine perioperative assessment, prior to initiation of anticoagulation, and as screening for admitted patients is low, with little to no change in patient management based on results of these panels. Coagulation testing should be considered in systemically ill patients, those with a prior history of bleeding or family history of bleeding, patients on anticoagulation, or patients with active hemorrhage and signs of bleeding. Thromboelastography and rotational thromboelastometry offer more reliable measures of coagulation function.ConclusionsLittle utility for coagulation assessment is present for the evaluation of chest pain, routine perioperative assessment, initiation of anticoagulation, and screening for admitted patients. However, coagulation panel assessment should be considered in patients with hemorrhage, patients on anticoagulation, and personal history or family history of bleeding.     

Concentration of citrate anticoagulant in peripheral blood progenitor cell collections

BACKGROUND: Peripheral blood progenitor cell (PBPC) collection by hemapheresis has become widely used in recent years. For anticoagulation during cytapheresis, citrate solutions, commonly ACD-A, are used, at a recommended anticoagulant-to-whole blood ratio of 1:11 to 1:12. Although the apheresis procedure is generally well tolerated, the most common patient complaints are attributable to transient hypocalcemia, which is a side effect of the citrate anticoagulant. Patients experiencing discomfort due to hypocalcemia are sometimes managed by a decrease in the flow rate of the anticoagulant. CASE REPORTS: Two cases are reported in which seemingly minor reductions in the anticoagulant: whole blood ratio appeared to cause gelation of freezing solution prepared from plasma that was collected in addition to PBPCs for use in the cryopreservation of cells. In both cases, the final ratio of citrate anticoagulant to whole blood was less than 1:12. Gelation occurred when plasma collected under these conditions was used to prepare freezing solution. CONCLUSION: The addition of heparin to this plasma, or the addition of ACD-A to correct the anticoagulant:whole blood ratio, prevented the gelation of freezing solution, which suggests that coagulation activation in the autologous plasma specimen was implicated in the subsequent gelation. During cytapheresis for PBPC collection, citrate-containing anticoagulants should be used at the recommended ratio of 1:12, or with more anticoagulant than usual. Tolerance for a reduced concentration of citrate may be more limited than is generally appreciated. When plasma is collected in addition to PBPCs, heparin should be added to both the cells and the plasma as soon as possible after the collection. Patients undergoing PBPC and stem cell collection should be given supplemental calcium, rather than less anticoagulant, to alleviate the discomfort associated with citrate.     

Controlled study of citrate effects and response to i.v. calcium administration during allogeneic peripheral blood progenitor cell donation

BACKGROUND: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors. STUDY DESIGN AND METHODS: Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.0-2.2 mg/kg/min). RESULTS: During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate. CONCLUSIONS: Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures.     

Leukocyte Elastase Release during Blood Coagulation: A POTENTIAL MECHANISM FOR ACTIVATION OF THE ALTERNATIVE FIBRINOLYTIC PATHWAY

Immunological detection of elastase, an enzyme present within leukocyte granules, has been used as a marker for polymorphonuclear leukocyte activation. Polymorphonuclear leukocytes contained 4.6 μg/10⁷ cells, whereas erythrocytes, mononuclear cells, and platelets contained <1% of this level. In plasma that was separated from blood cells after 1 h at 22°C, the mean level of elastase-related antigen in seven normal donors was 25±6 ng/ml. This level was unaltered by immediate separation of the plasma from the cells, by inclusion of protease inhibitors, or by anticoagulation of the plasma with either EDTA or acidcitrate-dextrose (the level in heparinized plasma was approximately threefold higher). In serum, the level of elastase-related antigen was 288±125 ng/ml, representing an 11.5-fold increase above plasma levels. The antigen detected in serum was immunochemically indistinguishable from the leukocyte enzyme. Release of elastase was observed when isolated polymorphonuclear leukocytes were added to nonanticoagulated platelet-rich or platelet-poor plasma, recalcified plasma, or to serum. Addition of a chelating agent to serum prevented elastase release, but calcium or magnesium did not induce release in the absence of plasma. Coagulation induced by addition of thrombin to plasma also failed to induce release. In whole blood or in anticoagulated plasma reconstituted with polymorphonuclear leukocytes and then recalcified, initial release of elastase occurred concomitantly with or slightly after clotting and reached maximal levels within 20-40 min after clot formation. The data indicates that early events in coagulation or other pathways that occur in parallel with coagulation induce leukocyte release. The release of elastase, a major fibrinolytic protease of leukocytes, from the cells provides a mechanism for this enzyme or other granule proteases to participate in physiological events.     

The impact of citrate concentration on adhesion of platelets and leukocytes to adsorbents in whole blood lipoprotein apheresis

Lipoprotein apheresis is applied to deplete low density lipoprotein and other apolipoprotein B containing lipoproteins in patients with severe familial hypercholesterolemia, hypertriglyceridemia associated pancreatitis, or lipoprotein (a)‐hyperlipoproteinemia. Anticoagulation of the extracorporeal circuit may influence cellular activation, as evidenced by a reduction of inflammatory parameters during regional citrate anticoagulation with acid citrate dextrose A (ACD‐A) commonly used in whole blood lipid apheresis. While the citrate concentration in the extracorporeal circuit has to ensure efficient anticoagulation, citrate infusion into the patient should be limited to avoid citrate overload. We assessed the influence of citrate concentration on cellular activation during in vitro circulation of whole blood containing 2.8 mM citrate (ACD‐A 1:40), 5.6 mM citrate (ACD‐A 1:20), or 13 mM citrate over polyacrylate‐based adsorbents for lipoprotein apheresis. We found increased platelet adhesion for anticoagulation with 2.8 mM citrate as compared to 5.6 or 13 mM citrate, as shown by cell counting and confirmed by scanning electron microscopy of adsorbent beads as well as by elevated levels of platelet activation markers and of platelet‐derived microvesicles. Leukocytes showed an equivalent adhesion pattern, while red blood cells remained unaffected at all citrate concentrations. Passage of blood over two consecutive columns resulted in enhanced platelet adhesion to the second column, presumably due to upstream preactivation. In conclusion, citrate influences activation and adhesion of platelets and leukocytes in a concentration‐dependent manner, and ACD‐A 1:20, equivalent to a citrate concentration of 5.6 mM in whole blood, ensures minimal cellular activation during passage of whole blood over polyacrylate‐based adsorbents.     

慢性阻塞性肺疾病急性加重期抗凝干预的临床研究

目的 探讨慢性阻塞性肺疾病(COPD)患者急性加重期应用低分子肝素钙对患者的肺功能和凝血功能的干预作用.方法 选择我科2009至2010年住院的COPD急性加重期患者70例,按随机原则分为对照组32例和抗凝组38例.对照组患者给予吸氧、抗感染、解痉平喘、止咳化痰治疗,抗凝组在对照组常规治疗的基础上加用低分子肝素钙,4100 U AXa/次,腹壁皮下注射1次/12 h.2组均10d为1个疗程.2组均于治疗前后检测肺功能和凝血功能.结果 治疗后2组的肺功能及动脉血气指标均显著优于治疗前(抗凝组:t =8.2064,6.9207,9.4351,7.5845,7.5241;对照组t=5.5588,3.0795,3.9374,2.8488,2.7726,P均＜0.01),但抗凝组改善程度显著优于对照组(t=3.2732,4.0167,7.3392,2.2528,3.0008,P均＜0.01);治疗后抗凝组的D-D含量及凝血指标(INR、PT、APTT、FIB)改善均显著优于治疗前(t值分别为5.721、23.235、25.318、23.841、11.354,P均＜0.01)和对照组(t值分别为7.738、19.365、23.373、21.008、9.712,P均＜0.01),而对照组治疗前后比较改善程度差异无统计学意义(P均＞0.05).抗凝组中无严重不良反应发生.结论 常规治疗虽能使COPD患者得到改善,但无法有效地改善患者血液的高凝状态.常规治疗联合低分子肝素钙抗凝治疗,在改善患者凝血功能同时能更好的改善患者的肺功能.     

33例危重患者枸橼酸抗凝床旁血滤治疗护理观察

目的观察枸橼酸抗凝血滤患者的临床情况，提出护理要点和策略，以达到安全和有效血滤的目的。方法对33例采用枸橼酸抗凝床旁血滤患者的临床情况进行总结。观察平均血滤时间、出血并发症及肌酐变化的情况等。结果患者的血滤时间达到（55．4±14．7）h，出血并发症极少，血滤所达到的溶质清除作用明显，72h后肌酐平均降低值（302．6±58．6）μmol／L。72h血滤后患者各项生理指标均有改善，出血并发症很少。结论枸橼酸抗凝床旁血滤滤器使用时间长，患者出血风险极低，可以达到较好的溶质清除效果。     

Regional citrate anticoagulation during continuous hemofiltration in cardiosurgical patients

Different citrate anticoagulation protocols are widely used during continuous renal replacement therapy. The investigation was to study the efficiency and safety of citrate coagulation in patients after cardiovascular interventions. Thirty-eight patients underwent continuous hemofiltration (CHF) with anticoagulation with 0.2% Prismocitrate 10/2 solution by the protocol of the company (Gambra Medical) after operations on the heart and large vessels. The clinical data, changes in azotemia, blood electrolytes and gases, as well as the mean values of citrate anticoagulation, and mean hemofilter life span were studied. The mean duration of citrate anticoagulation was 68 +/- 13.7 hours and its maximum duration wa 18 days. Predilution administration of Prismocitrate 10/2 along with postdilution replacement with routine solutions ensured the CHF dose of 35 ml/kg/hr. But for terminal conditions, volume metabolic control and effective anticoagulation were achieved without negative metabolic sequels and clinical complications. The mean life span of a hemofilter, with its mandatory replacement every 35-48 hours, was 40 hours. It is concluded that Prismocitrate 10/2 anticoagulation is an effective, safe, and easy-to-use method for CHF after cardiosurgical operations, which may be widely recommended when use of heparin is contraindicated.     

不同抗凝方式下连续组静脉-静脉血液滤过透析治疗对凝血及透析滤器使用寿命的影响研究

目的观察低分子肝素全身抗凝和枸橼酸局部抗凝在连续性静脉-静脉血液滤过透析(CVVH)时滤器使用寿命的比较研究。方法回顾性分析2016年1-4月54例患者行128例次CVVH的治疗情况,按照抗凝方式不同分为枸橼酸钠组和低分子肝素组,对两组患者的临床资料、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、滤器使用时间及疗效进行比较。结果两种抗凝方式下均取得显著疗效,枸橼酸钠组滤器及管路平均使用寿命显著长于低分子肝素组。结论枸橼酸局部抗凝技术在延长滤器使用时间方面有明显优势,且对患者凝血指标影响较小。     

两种不同抗凝方法在连续性静脉静脉血液透析滤过中应用的对比研究

目的观察连续性静脉静脉血液透析滤过（CVVHDF）治疗中常规肝素抗凝与体外枸橼酸钠抗凝两种方法的效果与特点。方法多器官功能不全病人70例,按照随机原则分为两组：A组（体外枸橼酸钠抗凝组）（n=37）,B组（常规肝素抗凝组）（n=33）行连续性静脉静脉血液透析滤过治疗,记录治疗前、后的血电解质,酸碱度,凝血指标的变化。管路及血滤器的凝血情况和使用时间,并观察治疗中不良反应。结果治疗过程中两组患者生命体征平稳,电解质、血气指标稳定,肌酐、尿素清除效果明显,超滤可达目标值,A组血滤器的凝血情况和使用时间优于B组,A组体内凝血时间不受影响,A组葡萄糖酸钙用量明显大于B组。结论在CVVHDF体外枸橼酸钠抗凝对比常规肝素抗凝更有效和更安全。     

Substitution therapy with prothrombin complex concentrates in acquired coagulation disorders

Over the past 11 years two different plasma concentrates--Prothromblex500 (factor II, IX and X) and Prothromblex Total500 (factor II, VII, IX and X) have been used in the treatment of 246 patients with acquired coagulation disorders, in particular deficiencies of the prothrombin complex (factor II, VII, IX and X). Patients on oral anticoagulation or suffering from liver disease required substitute therapy for severe bleeding episodes, acute operations or invasive diagnostic procedures. Serial coagulation studies and analyses showed that both concentrates achieved adequate correlation of the abnormal coagulation, whereby better results were obtained in patients on oral anticoagulation than in patients with severe liver disease. All operations and diagnostic procedures were completed without haemorrhagic complications, whilst the patients admitted for a severe bleeding episode were rapidly brought under control. These plasma concentrates did not cause any side effects. No case of intravascular coagulation was observed following substitution therapy.     

枸橼酸抗凝在妊娠合并重型肝炎患者血浆胆红素吸附治疗中的作用及护理

目的 探讨枸橼酸抗凝在妊娠合并肝炎患者血浆胆红素吸附治疗中的作用.方法 对该院25例妊娠合并重型肝炎患者用枸橼酸抗凝行血浆胆红素吸附串联血浆灌流进行治疗.结果 25例患者经治疗与护理85次,除1例治疗1 h后出现过1次滤器Ⅲ度凝血需更换血路管及灌流器,其余84次均顺利完成.全部患者痊愈或好转出院,其中17例肾功能恢复正常,15例产前发病的患者中2例围生儿死亡,5例早产儿预后良好.结论 应用枸橼酸抗凝行血浆胆红素吸附治疗与血液灌流治疗相互结合后,各项肝功能指标均有明显改善.     

Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution

ABSTRACT: INTRODUCTION: Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. METHODS: In high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid.Statistical analysis was performed using the Student t-test or analysis of variance (ANOVA) with post-hoc tests, Wilcoxon or Kruskal-Wallis tests for non-parametric analysis, and Kaplan-Meier survival analysis with Log Rank test. RESULTS: Thirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca++ were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation. CONCLUSIONS: RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.