1 Stanford, CA, USA 2 Innsbruck, Austria
EditorThe letter by Innerhofer and colleagues1 has reference. While, in reply, Drs Ng and colleagues2 have addressed most of the issues, I believe that it is important to emphasize some of the matters arising from their correspondence.
The most important point is that, when looking at the effect that haemodilution has on coagulation, the undiluted blood is the control for the coagulation seen in the sample after dilution. As a result, it does not matter what the reading was to start with, as one is looking at the change of coagulation that haemodilution brings about, no matter what the existing clinical setting is. Having an undiluted control was omitted by Innerhofer and colleagues3 in a recent paper, where they looked at the effect on coagulation of a crystalloid/colloid mixture vs a crystalloid control, and when the first measurement was taken only after the patient had received 500 ml of crystalloid as a preload for the spinal/epidural. This makes it difficult to comment on the absolute effect of dilution on coagulation, as the point of reference is not defined. It was recently shown that the regional anaesthesia co-load fluid itself has an effect on coagulation.4
Another point to be addressed is the old thought about the intrinsic and extrinsic coagulation pathways being separate. In fact, it is only Factor XII that needs external stimulation, while Factor IX is directly activated to IXa by TF/VIIa, thus ensuring a direct interaction between the extrinsic and intrinsic pathways.5 As a result, the TEG® is not only measuring the intrinsic coagulation pathway, but coagulation as a whole.
In closing, it must be added that Janvrin,68 and Ruttmann9 are not the only authors commenting on a possible clinical effect. This has been done by several others.1012 I believe that the work by Ng and colleagues is established fact. Whether there is a clinical effect, much like smoking has on clotting,1315 needs to be established.
T. G. Ruttmann
Stanford, CA, USA
EditorThank you for the opportunity to reply to Dr Ruttmanns letter regarding our correspondence with Dr Ng and colleagues on coagulation during i.v. fluid administration.1 Dr Ruttmann assumes that our recently published data on coagulation during i.v. administration of crystalloids/colloids or exclusively crystalloids for knee replacement surgery3 are not conclusive, because the point of reference was not defined. We agree with Dr Ruttmann that undiluted blood is needed as a control when coagulation in diluted blood is measured in vitro. But in the clinical setting, which we were studying, when precisely is a patient neither diluted nor hypovolaemic? If Dr Ruttmanns assertion was true, our baseline measurement obtained after patients had received 500 ml lactated Ringers solution (to correct hypovolaemia induced by starvation and a routinely used laxative) should have shown an already accelerated coagulation profile in all patients. This was not the case as our baseline measurements were all within the normal range. In addition, if crystalloid fluids enhance coagulation, we should have observed increased signs of hypercoagulability at the later measurement points B, C and D, after further crystalloid fluids had been administered. In fact, clot firmness decreased after administration of crystalloids/colloids or solely crystalloids and measurement of the -angle changed only marginally over time within groups. Furthermore, the suggested imbalance in AT III concentrations was not observed in our study. Instead, AT III concentrations were better maintained with the exclusive administration of crystalloids rather than the combination of crystalloids and colloids. If crystalloid fluid enhances thrombin generation, increased concentrations of thrombinantithrombin complex (TAT) and D-dimer (DD) should be detectable after administration of crystalloids. Interestingly, not even Dr Ruttmann made this observation in his own study in vascular surgery patients.4 In that study, thrombelastographic indices of initiation of coagulation and clot firmness were enhanced with crystalloids, while at the same time concentrations of TAT and DD were even lower in the crystalloid group as compared with the colloid group, although differences were not statistically significant and measurements might have been influenced by sampling blood from an indwelling i.v. line.16 Interestingly, a recently published in vitro study17 reported that haemodilution of blood with crystalloids or colloids causes a decrease in the activity of clotting factors. If molecular markers of activated coagulation are unchanged, and the activity of clotting factors and the platelet count are decreased, it is very difficult to accept shortened r- and k-times and an increased
-angle and maximal amplitude as an in vivo activation of coagulation initiated by administration of crystalloid fluids. We hypothesize that these thrombelastographic signs of hypercoagulability demonstrate an in vitro phenomenon provoked by sedimentation of red cells in diluted blood probes. It seems that this influence of red cells on clot formation becomes apparent when thrombelastographic measurements are performed without extrinsic activation. Of course, in vivo, coagulation factors of the extrinsic and intrinsic pathways can interact, and the prothrombinase complex is ultimately formed. As long as blood is not exposed to foreign surfaces however, activation through tissue factor predominates in vivo. What we wanted to say in our previous letter is that classic as well as rotation thrombelastography are ex vivo tests. Under these ex vivo conditions, tissue factor activates clot formation faster than in the presence or absence of intrinsic activation in vivo, which should be considered when different measurement methods are compared.
P. Innerhofer
D. Fries
A. Klingler
W. Streif
Innsbruck, Austria
References
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