Panacea Journal of Medical Sciences

Introduction

Therapeutic plasma exchange (TPE) is a procedure in which patient’s blood is passed through a automated cell separator where blood is being centrifuged and separates plasma from other components of blood.^[1] The plasma is then removed, disposed of, and replaced with either a colloid solution or a combination of crystalloid and colloid solutions.^[1] The selection of replacement fluid can have a significant impact on the therapeutic plasma exchange (TPE) outcome for high volumes. TPE can result in bleeding diathesis in recipients of renal transplants by altering the platelets and coagulation system, which are already significantly altered.^[2]

If only albumin is used as replacement fluid after TPE, there is a significant decrease in fibrinogen, other procoagulants, and anticoagulant proteins as evidenced by the prolongation of the activated partial thromboplastin time (aPTT) and prothrombin time (PT), even though there are no severe hemorrhagic episodes following TPE procedures.^[3] After TPE, the majority of coagulant proteins recover to 85–100% normal in a day, whereas factor X and fibrinogen take two days to recover.^[4], ^[5], ^[6]

A point-of-care tool thromboelastography (TEG) uses changes in viscoelastic properties during the clotting process. With a graphic depiction of the fibrin polymerization, TEG provides information regarding the dynamics of clot formation, strength, and stability.^[7], ^[8], ^[9] Because TEG can provide data at the patient's bedside in less than ten minutes, it has been validated as a tool for managing perioperative bleeding. TEG may lessen the number of needless haemostatic blood product transfusions and help medical professionals differentiate between coagulopathy and surgical bleeding causes. The test might also be used to prevent hesitancy in seeking help and lower the number of surgical reoperations brought on by bleeding. In the end, mortality could be decreased.^[10], ^[11], ^[12]

The management of bleeding during surgery and monitoring of coagulation activity of renal transplant recipients can be difficult. The standard tests like activated partial thromboplastin time(APTT) PT(partial thromboplatin time),International Normalized Ratio (INR) may not be as accurate as point-of-care (POC) assays like TEG, which measure the viscoelastic properties of blood.^[13] In order to more accurately estimate the patient's bleeding risk, coagulation is assessed in whole blood and includes interactions with red blood cells and platelets.^[13] This provides extra information on the patient's coagulation status.

Aim and Objective

Our study's objective is to examine the alterations in the coagulation profile as determined by TEG before and after plasma exchange using albumin as the replacement fluid with/without fresh frozen plasma.

Materials and Methods

A prospective comparative study was carried out in the Department of Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, from 1^st September 2016 to 31^st December 2017 in the patients of renal allograft recipient or post renal transplant with history of CKD. The study was done after approval from institution’s ethical committee.

Results

Total 47 patients with a history of CKD (pre-transplant and post-transplant) were included in the study who underwent a total of 71 TPE procedures as part of desensitization protocol. In 35 procedures (Group A) 5% albumin was used as a replacement fluid while in other 36 procedures (Group B) 5% albumin with FFP was used as a replacement fluid. There was no bleeding episodes during study period in group A and group B.

Discussion

In our study, no parameters related to patient demographics or TPE had the significance in the resulting outcome of two different replacement fluid strategy, however, age and gender variability is described by Sun et al. ^[14] In our study age difference did not reach a statistical significance, so it had no impact on result outcome.

In our study, compared to before TPE, patients TEG analysis after TPE procedure revealed a relatively hypocoagulable state when albumin only was used as a replacement fluid. The value of R (3.489±0.9136 vs 7.669±1.695) and K (3.09±0.50 vs 6.611±1.588) increased while alpha angle value (37.17±8.79 vs 34.92±7.564) decreased (p value< 0.001).The value of MA (36.55±12.09 vs 47.99±11.14) was suggestive of a relatively hypercoagulable state as its value increased after TPE procedure and TEG tracing did not reveal a true picture of the hypocoagulable state.Thölking et al,conducted a study on 10 patients using 5% albumin as replacement fluid and results were similar to our study. ^[15]

In another study by Blasi et al., 6 patients were treated with TPE with 5% albumin as replacement fluid.Clotting time (CT), maximum clot firmness (MCF), delay in clot formation, and reduction in clot firmness were all TEM parameters that fell below the usual ranges. ^[16] According to reports, the fibrinogen value decreased by 67% on average. This is due to the fact that fibrinogen, IgM, and a2-macroglobulin are primarily found in the intravascular compartment, and PE is highly effective in lowering these levels. This result was consistent with our investigation because the reaction rate (R) for TEG and the CT for ROTEM are both measured in minutes, or the amount of time it takes for the trace to attain an amplitude of 2 mm. and R value changed from hypercoagulable to normal state as per reference value and R time was prolonged after TPE in our study.

In our study, we suspected that increase in MA value after TPE procedure might be due to activation of PLT after coming into contact with the TPE equipment as MA measures the maximum strength (in millimeters) of the formed clot and primarily evaluates fibrinogen and platelets but further studies required to validate this point.Parikh et al. and Schoorl et al. also described the reduction in platelet count after TPE. ^[17], ^[18]

In our study, when FFP along with albumin was used as a replacement fluid, K value increased after TPE procedure but compare to table 4, K value increase was more pronounced (3.486 vs 0.39) when albumin alone was used as a replacement fluid (p value< 0.005) as high value of K commonly suggests the necessity for administration of cryoprecipitate or fibrinogen concentrates. However, no other studies have compared coagulation profile of TEG analysis in albumin and FFP as a replacement fluid with albumin alone as a replacement fluid in our best knowledge.

In our study while comparing the coagulation parameters it was obseved that there was a mean increase in R time after TPE with albumin and FFP as a replacement fluid (p value< 0.005). The mean increase in R was suggestive of hypocoagulable state and mean increase in alpha angle and MA value did not correlate with this finding. The mean increase in R value was more pronounced (4.18 vs 0.39) in TPE alone with albumin compare to TPE with albumin and FFP group (p value< 0.005).

It was suggested by Agarwal et al., and Tek et al. to monitor fibrinogen levels and to switch to plasma when they drop below 1.25 g/L. ^[19], ^[20] According to Feuring et al., FFP should be taken into consideration following PE if there is a history of hemorrhagic episodes or if fibrinogen fails to return to levels that are safe. ^[21] According to Lance et al. most patients have normal liver function, but even those with mild liver damage should use caution if they have cirrhosis. ^[22] Based on our observations, albumin usage is not recommended in liver patients at such high risk. According to Pilgeram et al. the condition of severe hypofibrinogenemia may last longer than it would given a fibrinogen production rate of 0.26–0.38 g/l per day. ^[23]

In our study group, there was a mean decrease in alpha angle after TPE with albumin only while mean increase after TPE noted in TPE with albumin and FFP (-2.25 vs +1.59) (p value <0.005). This might be due to fibrinogen factor in FFP which increased the alpha angle value after TPE procedure. As well as a mean increase in MA value was more in TPE with albumin and FFP compared to TPE with albumin only (+14.02 vs +11.44) (p value <0.005) and again fibrinogen factor might be responsible for this TEG tracing. Pre-transplant patients were hypercoagulable while post-transplant patients were hypocoagulable as TEG tracing showed in our study (3.28±0.61 vs 4.65±1.59) (p value< 0.001). Other parameters did not reach statistical significance except LY30%.

Sabovic et al., and Vaziri et al. described the coagulopathy in pre-transplant patients on multiple hemodialysis (MHD). ^[24], ^[25] As per Sabovic et al., compared to CKD patients who are not receiving dialysis, hemodialysis patients exhibit a moderation of the hypercoagulable profile, with a lower MA and an increased clot breakdown. In our study also pre transplant patients on MHD had decreased MA value (37.92±10.38) compare to reference value. ^[16], ^[17], ^[24]

Finding in our study was similar to these findings reported by Timmermans et al. as R value was lower in pre transplant patients (3.28±0.61) compare to post-transplant patients (4.65±1.59) (p<0.001).^[26] We could not establish the significance of LY30% value in TEG analysis before and after TPE procedures as 42 patients had no fibrinolysis in TEG analysis and there is no literature available on LY30% value significance in TPE procedures in best of our knowledge. Further studies are required to validate its significance in TPE procedurres.

Limitations

This study has small sample size single center study including CKD patients. We di not do standard coagulation tests to compare it with thromboelastography parameters. Significant intra- and inter-laboratory variability can arises from the lack of standardization in the approach for Kaolin Activated Whole Blood Thromboelastography.

Conclusion

Our observations led us to the conclusion that, in thromboelastography analysis, TPE with albumin alone without the inclusion of fresh frozen plasma can seriously disrupt blood coagulation. If albumin is the only replacement fluid used after a kidney transplant, the risk of bleeding increases. For CKD patients who are at a high risk of bleeding, thromboelastography seems to be a practical coagulation profile test.

Confict of Interest

None.

Source of Funding

None.