Method and apparatus for hemostasis and blood management6787363Abstract A procedure for hemostasis and blood management, particularly for cardiovascular procedures, provides: sampling instructions, i.e., when to draw blood samples and how to pre-treat the blood samples, a decision tree to assist the interpretation of hemostasis analysis results allowing for the identification of various coagulopathies, and treatment suggestions related to the hemostasis analysis results. The analysis, interpretation and identification may be conducted by a suitably programmed computer. Claims We claim: Description TECHNICAL FIELD
TABLE I
R R time is the period of time of latency from the time that the blood
was placed in the TEG .RTM. hemostasis analyzer until the initial
fibrin formation.
.alpha. measures the rapidity of fibrin build-up and cross-linking (clot
kinetics)
MA MA, or Maximum Amplitude, is a direct function of the maximum
dynamic properties of fibrin and platelet bonding via GPIIb/IIIa
and represents the ultimate strength of the fibrin clot.
LY30 LY30 measures the rate of amplitude reduction 30 minutes after
MA and represents clot lysis.
Of course, the procedure described herein may be adapted for use with hemostasis analysis machines that provide the above parameters, additional parameters or different parameters. Such machines are commercially available from various manufacturers. Referring to FIG. 5, a procedure 100 is outlined therein for hemostasis analyzer guided management of hemostasis and/or blood component usage, and to FIG. 6 wherein a decision tree 200 is defined to assist interpretation of the results provided by the hemostasis analyzer. The following description of a particular sampling protocol associated with a cardiovascular procedure provides an illustration example that may be used to develop additional sampling protocol for particular medical/surgical procedures. It will be appreciated that sampling protocols will necessarily be developed for each particular procedure, and that the described sampling protocol for a cardiovascular procedure may not be appropriate in connection with other procedures, such as for example, trauma treatment or organ transplantation. The sampling instructions in the procedure indicate that all blood samples are to be treated with low concentrations of kaolin. Kaolin is a reagent that acts as a control surface that activates Factor XII and platelets of a blood sample, which provides faster results without losing the sensitivity of measuring all phases of patient hemostasis or detecting low concentrations of heparin. Another issue in evaluating hemostasis and coagulopathy in connection with the herein described cardiovascular procedure is heparin effect. The sampling outlined in the procedure may call for use of heparinase--an enzyme that breaks down the heparin--so that patient hemostasis in the presence and absence of heparin can be measured. Some samples are split and analyzed with heparinase and some are analyzed without heparinase. Using this technique, it is possible to see if there is any heparin effect, residual heparin, or line contamination. If the results from both samples are similar, for example, both R values are within normal limits, then heparin has been effectively reversed. If, using the TEG hemostasis analyzer, R with heparinase is normal, but R without is elongated, then the heparin is not completely reversed. Note that if the patient has not been treated with heparin as part of the cardiovascular procedure, coagulopathy should be evaluated based on the sample without heparinase. One of the advantages of TEG.RTM. hemostasis analysis is that samples can be run simulating in vivo conditions in the sample cup--and should. So, in the case where the patient is not on heparin, hemostasis assessment should be based on the sample without heparinase. According to the exemplary cardiovascular sampling protocol 100 outlined in FIG. 4, samples are drawn at four time points: Baseline on induction At rewarming (about 36.degree.) Ten minutes post protamine Post surgery. Baseline Sample When the patient comes into the operating room a baseline sample is run as a starting point of the measuring stick for patient hemostasis and to establish whether the patient is hypercoagulable or has a tendency to bleed. This specimen is split into two aliquots, sample 1 and sample 2. One of the samples is analyzed using heparinase and one is analyzed without heparinase to check for heparin effect as well as for antithrombin III (ATIII) deficiency. Conveniently, the TEG.RTM. hemostasis analysis system allows for the use of plain sample cups and pins (clear cups) and sample cups and pins treated with heparinase (blue cups). ATIII deficiency is easily shown if the heparinase R and non-heparinase R are the same when heparin has been administered either to the patient or to the sample in the cup. ATIII deficiency is typically treated with ATIII or fresh frozen plasma (FFP). If the patient is hypercoagulable, antifibrinolytic drugs are contraindicated unless the patient has been treated with platelet inhibitors or has the tendency to bleed, in which case Aprotinin (Trasylol) is suggested. At Rewarming A sample, sample 3, is drawn at rewarming of the patient--approximately 36.degree.--and shows the maximum expression of any coagulopathy that has developed during the procedure. Sample 3 is another notch on the hemostasis measuring stick for two effects: the effect of the trauma of surgery on the patient the net effect of extracorporeal surfaces on hemostasis at a time when the blood has been on the pump for the longest time. Extra-corporeal devices, in general, reduce hypercoagulability, but in the case of off pump coronary artery bypass (OPCAB) the patient becomes more hypercoagulable. The results from sample 3 are typically used to determine which drug products are required (and are usually administered at this time), and which blood products should be ordered for administration later. The MA value of sample 3 is typically 5 to 7 mm lower at this point than the post protamine sample, described below, and this should be taken into consideration when evaluating the results. This is particularly true if the value is borderline low and platelets, which may not be needed, are being considered. Usually, if rewarming values are normal, patient hemostasis will continue to be normal post surgery. However, the patient should still be monitored for residual heparin effect (post protamine), surgical bleeding, or at a later time for hypercoagulability. 10 Minutes Post Protamine At this point, the patient has been treated with protamine to neutralize the heparin. This is a split sample, samples 4 and 5, used to compare the R with and without heparinase as a check for residual heparin. If the R's are equal for both sample 4 and sample 5, the heparin has been effectively neutralized. If the R without heparinase is longer than with, there is residual heparin. Samples 4 and 5 also show the importance of the baseline sample, since the degree of change from baseline is significant. Where the change between the baseline MA and the post protamine MA is great, that is, a baseline MA that is high and falls to the borderline transfusion trigger value, is a predictor of greater oozing or bleeding than where the difference is smaller, and should be considered for treatment accordingly. If the sample post protamine shows coagulopathy, most likely it is consistent with what was already observed while the patient was on the bypass pump. Post Surgery After surgery--one hour in the intensive care unit (ICU)--the sample provides a wealth of information. Perhaps the most important is that it is a check if treatment so far was effective. It is also the point at which to evaluate the amount of chest tube drainage and heparin rebound. If there has been an increase in the hypercoagulability, consideration should be given to whether to anticoagulate or to order more testing, such as at 2 hour intervals. If the hemostasis analysis results look normal, i.e., they do not indicate any coagulopathy, but the patient is bleeding, then there is likely no coagulopathy. It's most likely surgical bleeding. However, consideration should be given to von Willebrand's disease or acquired von Willebrand's factor (VWF) deficiency. In this case, the clot is fully functional, but it cannot adhere to the damaged vascular site, due to poor platelet-to-sub endothelial collagen bonding. Surgical bleeding can typically be differentiated from VWF deficiency by the greater rate of bleeding associated with surgical bleeding. However, because of the increased risk to the patient in misdiagnosing VWF deficiency as surgical bleeding, consider treating the patient with FFP or cryoprecipitate (cryo) (which carries VWF as part of Factor VIII) to confirm, or with desmopressin acetate (DDAVP) to stimulate the release of VWF by the endothelium. If the bleeding is diminished by treatment, VWF deficiency is indicated. If bleeding continues despite treatment, surgical bleeding is indicated, and the FFP or cryo is needed in any case for volume replacement. When the surgical site is small, surgical bleeding may be remedied clinically with continuous product transfusion, and this remedy should be considered before reexploration. If the site is large, reexploration may be required to remedy the problem. Thus, according to one procedure in accordance with the invention, samples are drawn at multiple time points, and these samples may be treated with kaolin to achieve faster analysis results. Comparison of heparinase treated samples to non-treated samples evaluates degree of heparin effect, residual heparin effect, heparin rebound, and patient hemostasis in the presence of heparin. Following this sampling protocol gives a complete picture ofthe patient's hemostasis as it shifts from baseline through surgery and into the ICU. These samples, when evaluated against the decision tree 200 (FIG. 6), provide additional answers regarding treatment of developing coagulopathies or surgical bleeding. While the above-described sampling protocol is primarily adapted for use in connection with a cardiovascular procedure, the decision tree 200 has general applicability to the diagnosis and treatment of coagulopathies. The decision tree 200 may be implemented as a guide associated with the blood hemostasis analyzer. Conveniently, the decision tree 200 may be implemented as part of the control program 34 used by the computer 30 to control operation of the blood hemostasis analyzer. Alternatively, the blood hemostasis analyzer may include communication capability and may communicate with a remote computing device, such as a remotely located computer, a handheld computer and the like, via the Internet or other communication network using wired and/or wireless connections. An arrangement of a blood hemostasis analyzer to communicate with a remote computer that may be used is described in the aforementioned U.S. patent application Ser. No. 09/974,044 the disclosure of which is incorporated herein. The decision tree 200 helps identify the coagulopathy and in the case of hyperfibrinolysis, can distinguish between primary and secondary fibrinolysis. In the case of hypercoagulability, it may be necessary to use a hemostasis analysis technique that can distinguish between platelet-induced vs. enzymatic hypercoagulability. The TEG hemostasis analysis system allows for making this distinction. In applying hemostasis analysis results to the decision tree 200, the first evaluation is for hyperfibrinolysis. Using TEG hemostasis analysis, there is an indication of hyperfibrinolysis where LY30>7.5%. If LY30 isn't yet available, EPL--an estimate of lysis--may be used instead, with a value of >15% indicating fibrinolysis (202). If the sample shows fibrinolysis next the coagulation index (CI) is evaluated (204). If the coagulation index is less than one, CI<1 (206), the patient is not hypercoagulable, and this is primary fibrinolysis (208). If the sample shows fibrinolysis and the coagulation index is greater than 3, CI>3 (210), indicating hypercoagulability, then it is secondary fibrinolysis (212)--it is secondary to the hypercoagulability. Making the determination of primary fibrinolysis then becomes easy--if it is not secondary primary fibrinolysis (212), it is primary (210). The D-dimer test is frequently used to diagnose fibrinolysis, but it gives an elevated result for both types of fibrinolysis, and this is extremely risky. It leads to a misdiagnosis, and the penalty to the patient of misdiagnosing secondary fibrinolysis as primary can be fatal. For example, suppose a mistaken diagnosis of secondary fibrinolysis is treated with antifibrinolytics such as Amicar. This treatment in effect blocks the pathway to break down the clot and therefore increases the probability of a repeat ischemic event. On the other hand, if a mistaken diagnosis of secondary fibrinolysis is treated with anticoagulants--making the patient bleed more--the penalty is not as great. Continued or increased bleeding can be neutralized with drugs, as in neutralizing heparin with protamine. Antifibrinolytic drugs such as Amicar may then be given to treat the primary fibrinolysis. On the other branch of the decision tree 200, when LY30<7.5 (202) (no hyperfibrinolysis), evaluation is made first for hypercoagulability. A coagulation index greater than 3, CI>3 (214) indicates hypercoagulability. The next step is to decide between enzymatic and platelet hypercoagulability. If using the TEG.RTM. hemostasis analysis system a check of R is made. If R is short, for example less than 4 minutes (216), it's enzymatic (220). In addition, if R is short (216) and platelet function is high, MA is high, greater than 73 mm (218), it is due to high enzymatic reaction and high platelet activation (222). On the other hand, if R is normal and MA is high, hypercoagulability is due to high platelet function (224). Treatment with platelet inhibitors such as aspirin, ADP inhibitors such as Plavix, or GPIIb/IIIa inhibitors such as ReoPro, Integrilin, and Aggrastat is indicated. When CI<3 (214)--not hypercoagulable--and R is elongated, greater than 10 minutes (226) the first priority is to normalize the R. This long R is due to low clotting factors (228) from coagulopathy or hemodilution resulting in a low rate of thrombin formation, which activates the platelets and cleaves the soluble fibrinogen into fibrin. The best treatment is FFP for clotting factors. If R is normal--no hypercoagulability--and MA is <45 mm (230) indicating low platelet function (232), typical treatment is with DDAVP or one unit of platelets. If MA<48 mm, platelets should be administered appropriately as described below. If R and MA appear normal, but alpha is low (a<45.degree., 234), you can correct for low fibrinogen level (236) by treating with cryo, which not only contains high concentrations of fibrinogen, but also has high concentrations of factor VIII and factor XIII. In some situations, R may be slightly elongated post protamine due to hemodilution. In such cases, the patient is usually not bleeding and no treatment is needed. If the hemostasis analysis results are normal but the patient is still oozing, that should gradually diminish. The decision tree 200 arranges the evaluation criteria in a logical manner and is used to arrive, in a systematic way, at a coagulopathy diagnosis. All the hemostasis parameters are interdependent, and it is necessary to evaluate the parameters relative to each other, in addition to the patient's clinical status and bleeding state, to determine if a coagulopathy is present, which coagulopathy it is, and how to treat it. FIG. 7 illustrates a treatment guide 300 that maybe part of the protocol to assist in this last step. Referring to FIG. 7, the treatment guide 300 provides guidance and a treatment suggestion based on hemostasis analysis results. Knowing the part of the hemostasis process that is represented by each of the parameters leads to the hemostasis state of the sample, and, thus, knowing the magnitude of a parameter indicates the level of coagulopathy. Having identified this, then appropriate treatment in the right dosage becomes easier to determine. As an illustration, using the decision tree, an R value over 10 mm indicates low clotting factors. The treatment guide 300 expands on that and indicates that R between 11 and 14 shows slightly low clotting factors and should be treated with 2 units of FFP, while R>14 indicates more severe shortage of clotting factors and should be treated with twice that--4 units of FFP. Similarly, MA values less than 55 mm indicate low platelet function and three categories of MA are shown for increasing levels of platelet dysfunction, with corresponding increasing therapy. Slightly low levels can be treated with DDAVP, one unit of platelets, or nothing at all as it may be possible to simply wait for the patient's own platelets to recover. The treatment guide 300 gives specific guidance in how to treat the coagulopathies that are already present or develop during and after surgery. The degree of coagulopathy can be evaluated by the magnitude of the hemostasis analysis values reported, and treatment determined and adjusted based on those values. The decision tree 200 and treatment guide 300 may be further used to test potential treatment protocols prior to administering the treatment to a subject. The efficacy of a proposed treatment can be tested by adding the pharmaceutical or blood product to a blood sample in vitro. Prior in vitro evaluation of the treatment protocol can provide an indication of the efficacy on patient hemostasis in vivo. In this manner, hemostasis and blood product usage is managed by first testing according to a sampling protocol, determining a coagulopathy based upon a decision tree and identifying a treatment in view of a treatment guide. The propose treatment may then by tested in vitro to confirm efficacy. It will be appreciated that a post treatment sampling and testing protocol The invention has been described in terms of several preferred embodiments. One of skill in the art will appreciate that the invention may be otherwise embodied without departing from its fair scope, which is set forth in the subjoined claims.
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