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Patients with idiopathic thrombocytopenic purpura have safely undergone cardiac surgical procedures; however, platelets were transfused in 20 of 24 reported instances, and no point-of-care testing of coagulation status was performed. Herein, we report the case of a patient with idiopathic thrombocytopenic purpura who required urgent coronary artery bypass grafting and intra-aortic balloon pump support. Rotational thromboelastometry was used as a point-of-care test of the patient's coagulation status. No preoperative prophylactic transfusion of allogeneic platelets was necessary, and in fact the patient required no allogeneic blood products during his hospitalization. We believe that point-of-care coagulation tests such as thromboelastometry warrant further evaluation regarding their usefulness in the clinical decision of whether to transfuse platelets and other blood products.
Patients with idiopathic thrombocytopenic purpura (ITP) have safely undergone cardiac surgical procedures; however, platelets were transfused in 20 of 24 reported cases, and no point-of-care testing of the patients' coagulation status was performed.1-3 Here, we report the case of a patient with ITP who underwent urgent coronary artery bypass grafting with intra-aortic balloon pump (IABP) support. We discuss the use of rotational thromboelastometry as a point-of-care test of the patient's coagulation status.
In February 2009, a 47-year-old man with a tight ostial stenosis of the left main stem, an occluded right coronary artery, and normal ventricular function experienced a non-ST-elevation myocardial infarction and was referred to our hospital for urgent surgical revascularization. He was scheduled for urgent triple-vessel coronary artery bypass grafting.
The patient was in chronic remission from non-Hodgkin lymphoma. He had ITP, normal bone marrow, and no history of bruising or spontaneous bleeding. His platelet count upon hospital admission was 55,000/mm3. Preoperatively, his hemoglobin level was 15.1 g/dL (hematocrit, 45%). The international normalized ratio (INR) was 1.1, and the activated partial thromboplastin time (aPTT) was 16 sec (normal range, 20–25 sec). Various assays (described below) were performed by means of rotational thromboelastometry on a ROTEM® machine (Tem International GmbH; Munich, Germany). These showed an essentially normal coagulation profile (Figs. 1 and and2).2). We decided not to transfuse platelets preoperatively. An IABP was inserted before anesthesia was induced. Ringer injection was used for fluid replacement during the harvesting of 2 units of autologous blood by acute normovolemic hemodilution. Cardiopulmonary bypass (CPB) was established by means of a centrifugal pump and standard pump circuits, with systemic cooling of the patient to 32 °C. We administered an intravenous bolus of 400 IU/kg of unfractionated heparin so that an activated clotting time above 480 sec could be maintained during CPB. In total, 5 g of tranexamic acid was infused. The total bypass time was 76 min, and cross-clamp time was 44 min. After the heparin was neutralized with 0.8 mg of protamine sulfate per 100 IU of total heparin, the 2 units of autologous blood were returned. All fluid was warmed with use of a Ranger® Blood/Fluid Warming system (Arizant Inc.; Eden Prairie, Minn), and a forced-air warming device was used until the patient's nasopharyngeal temperature was above 36 °C.
Chest-tube drainage yielded 825 mL in the first 24 hours after the operation. The platelet count on the 1st day after surgery was 42,000/mm3. The IABP was removed on the 1st postoperative day by use of a FemoStop® Compression Assist Device (St. Jude Medical, Inc.; St. Paul, Minn). The patient was started on aspirin 24 hours after the operation. The minimum hematocrit measurement during his hospitalization was 27%. No transfusion of allogeneic blood products was necessary, and the patient was discharged from the hospital with a platelet count of 71,000/mm3 on the 5th postoperative day. Upon 6-week follow-up, he was experiencing no angina, dyspnea, or palpitations. His surgical wounds had healed well, and the sternum was stable upon palpation. He was referred to the care of his cardiologist and family physician.
Idiopathic thrombocytopenic purpura is a bleeding condition of unknown cause in which the blood fails to clot adequately because of a low circulating platelet count (often <50,000/mm3) and a shortened platelet lifespan. Patients with ITP can present with a range of symptoms, from none at all to the classical pattern of petechiae and purpura. The cause of thrombocytopenia can be autoimmune rather than idiopathic: antibodies against platelets are detected in approximately 60% of patients.4 Most often, these are antibodies to platelet membrane glycoproteins IIb/IIIa or Ib-IX, and are of the immunoglobulin G (IgG) type. Coating platelets with IgG renders them susceptible to opsonization and phagocytosis by splenic macrophages. Although successful cardiac operations have been reported in patients who have ITP, platelets and other blood products have often been transfused.1 In accordance with the published reports of cardiac surgery in patients with ITP, no point-of-care tests of coagulation have been available. Thromboelastometric tracing makes such testing possible.
According to national United Kingdom guidelines,5 our patient had a platelet count that warranted prophylactic platelet transfusion before major surgery. However, his preoperative thromboelastometric results were essentially normal. Although abnormal thromboelastometric results have a low specificity for predicting bleeding,6 a normal tracing indicates adequate activation of the coagulation cascade and fibrin formation (secondary hemostasis). Therefore, our patient was given no prophylactic transfusion of platelets. His postoperative platelet count was 42,000/mm3, and the total drainage loss was 825 mL. The postoperative thromboelastometric results were only slightly abnormal (Figs. 3 and and4).4). These factors—in the clinical context of a hemodynamically stable patient with a bleeding rate of less than 100 mL/hr—did not indicate a need for allogeneic transfusion.
Routine testing of platelet count, INR, and aPTT is only slightly correlated with actual perioperative blood loss.7 Conversely, thromboelastometry is a more physiologic method of measuring hemostatic function.8 Unlike laboratory tests of hemostasis that are measured in plasma, thromboelastometry measures clotting in whole blood and, accordingly, the interaction between fibrinogen, platelets, and the protein coagulation cascade. Thromboelastometry measures the viscoelastic properties of blood while the blood is being induced to clot in a low-shear environment that resembles sluggish venous flow. This enables the determination of the kinetics of clot formation and growth, in addition to the strength and stability of the formed clot.
The generic name for this technology was “thromboelastography” until Haemoscope Corporation copyrighted the TEG® Thrombelastograph® Hemostasis Analyzer (Haemonetics Corp.; Braintree, Mass). The term then became “thrombelastography.” Tem International GmbH's alternative machine, ROTEM®, performs rotational thromboelastometry.
The process of thromboelastometry begins when 0.2 mL of citrated blood is placed into a disposable plastic cup (diameter, 8 mm) by use of a computer-controlled electronic pipette. Reagents and controls are added to the same cup, which is contained in a robust metallic cup-holder. The pipetting takes less than 1 minute to complete. The cup-holder is then placed into the ROTEM machine's measurement channel, which consists of a fixed cylindrical cup and a permanently oscillating vertical axis. The axis oscillates alternately to the left and to the right (± an angle of 4.75°). The motion is detected by an optical system and is analyzed by means of dedicated computer software. If clotting occurs, the movement is obstructed, and as the clot becomes firmer, the rotational amplitude of the axis is reduced.
Rotational thromboelastometry is quick to perform and easy to interpret. The ROTEM's output is a graph. After 30 minutes, the graph shows results that are adequate for interpretation; it takes up to 1 hour to be fully produced. The strength of a clot is graphically represented over time in a cigar shape. The width of the graph at any point shows the clot strength or elasticity. A “weak” clot is graphically expressed as a narrow thromboelastogram; a “strong” clot, conversely, is shown as a wide one.
Rotational thromboelastometry includes various assays that are activated differently, depending upon the test. One assay, INTEM, uses contact activation of coagulation via the intrinsic pathway and therefore depends on coagulation factor XII. INTEM is also useful in determining adequate protamine reversal. The EXTEM test uses tissue factor and is more physiologic than INTEM. The HEPTEM assay is an INTEM test with the addition of heparinase. In FIBTEM, differentiation between platelet function and the fibrin polymerization process is possible, because the FIBTEM reagent eliminates platelet function by means of a powerful platelet inhibitor (cytochalasin D). Whereas clots obtained by means of EXTEM or INTEM are composed of platelets and fibrin, the clot obtained in the FIBTEM assay is primarily a fibrin clot. The difference in maximum clot firmness between the FIBTEM assay and either the EXTEM or the INTEM assay is the contribution that is made by activated platelets.
Figure 5 shows an example of an INTEM graph. Five values are measured upon the completion of tracing. Clotting time (CT/r) is a measure of the time that it takes for clotting to begin; it is similar to a whole-blood clotting time. Clot formation time (CFT/k) and the α angle indicate how fast the clot strength is increasing after clotting has begun. The α angle is defined as a tangent to the clotting curve through the 2-mm point. It is reported in degrees and represents the angle between the slope and the baseline. A reduced CFT or α angle may be due to any combination of coagulation deficiencies, reduced platelet function, and reduced platelet count. Maximum clot firmness (MCF, or maximum width of the graph) is an indication of the maximum attainable clot strength. Decreases in MCF are associated with reduced platelet function or numbers, reduced fibrinogen levels, or both. Maximum lysis (ML, the percentage of MCF) is the reduction of the clot firmness after MCF in relation to MCF stability of the clot (ML, ≤15%) or fibrinolysis (ML, >15%) within 1 hour. Maximum lysis is also indicated as A (amplitude) at different time intervals: A20 (amplitude after 20 min) and A25 (amplitude after 25 min) are measures of fibrinolysis.
Figure 5 shows a normal result: rapid clot onset (short CT), rapid clot formation (short CFT and large α angle), normal amplitude (MCF), and no change in A25.
The correlation between platelet count and hemostasis is not linear or predictable. Despite this, some believe that a count below 50,000/mm3 denotes a risk of massive surgical bleeding.9 Recent studies suggest that higher concentrations of fibrinogen can compensate for thrombocytopenia and ensure adequate hemostasis.10 Of note in the case of our patient, no allogeneic products were transfused in what looked, on paper, to be strong circumstances for prophylactic platelet transfusion. His hemostasis was efficient, as thromboelastometry showed preoperatively, and in fact he required no allogeneic transfusion throughout his hospitalization despite the need for preoperative IABP support. We believe that further studies are warranted in order to evaluate the true benefit of prophylactic platelet transfusion and the more extensive use of point-of-care coagulation tests—such as thromboelastometry—as guides for clinicians who must decide whether to transfuse blood products.
Address for reprints: Michele Rossi, MD, Department of Cardiac Surgery, Royal Sussex County Hospital, Eastern Rd., Brighton BN2 5BE, UK