Evaluation of the coagulation system

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Evaluation of the coagulation system

Craig M. Combs, MD and Robert M. Craft, MD

Evaluation of the coagulation system may be useful for the preoperative assessment of coagulation status and measurement of anticoagulation therapy, as well as the diagnosis and management of intraoperative coagulopathy. The dual-cascade concept of coagulation, which involves the intrinsic and extrinsic pathways, is now understood to be an inadequate and incomplete representation of in vivo coagulation. The three-stage process of actual in vivo coagulation (activation, amplification, and propagation) involves complex interactions among the vascular endothelium, tissue factor, platelets, and soluble clotting factors. However, the classic dual-cascade view may still be beneficial in providing a reasonable model of in vitro coagulation tests, that is, the activated partial thromboplastin time (aPTT) and prothrombin time (PT) (Figure 147-1).

Preoperative assessment

The best method to screen patients preoperatively for bleeding disorders remains a thorough clinical history. Routine coagulation testing is not warranted without indications. Clinical indications for testing include congenital or acquired bleeding disorders, excessive bleeding during previous operations, liver disease, and the use of drugs or supplements with anticoagulant properties. Table 147-1 summarizes the most common preoperative coagulation studies used for assessing the coagulation status of patients.

Table 147-1

Studies Commonly Used Preoperatively for Assessing Patients’ Coagulation Status

Test Measured Aspect Comments
PT Extrinsic pathway and common pathway The PT is prolonged if any of factors VII, X, V, II, and I are deficient, abnormal, or inhibited.
The coagulant activity of these factors must be <30% of normal and the fibrinogen concentration must be <100 mg/dL for the PT to be prolonged.
The PT may be used as a screening test for patients on oral anticoagulant therapy.
The PT may be used to assess the synthetic function of the liver.
aPTT Intrinsic pathway and common pathway The aPTT is prolonged when any of factors XII, XI, IX, VIII, X, V, II, and I are deficient, abnormal, or inhibited.
The coagulant activity of these factors must be <30% of normal and the fibrinogen concentration must be <100 mg/dL for the PT to be prolonged.
The aPTT is prolonged by heparin therapy.
The aPTT is prolonged in hemophiliacs and, usually, in people with von Willebrand disease.
Fibrinogen Fibrinogen level; common pathway Levels <100 mg/dL may be associated with the inability to form a clot and severe bleeding.
Platelet count Quantitative platelet assessment The platelet count does not provide information regarding platelet function.
Thrombocytopenia is defined as a platelet count <150,000/μL.
Bleeding during surgery may be severe in patients with platelet counts of 40,000-70,000/μL.
Spontaneous bleeding is unlikely to occur if the platelet count is >10,000-20,000/μL.
Bleeding time Platelet function assessed by evaluating the time for a platelet plug to form after vascular injury Bleeding times are prolonged in patients with platelet dysfunction (e.g., patients on aspirin therapy or those who are uremic).
Owing to the techniques used for the test, reproducibility is poor, and results are imprecise.
The bleeding time is not useful for routine screening.
Platelet aggregometry Assesses the ability of platelets to aggregate after exposure to ADP, epinephrine, collagen, or ristocetin Only qualitative results (clot retraction versus no clot retraction) are reported.
Quantitative results are difficult to obtain.

ADP, Adenosine diphosphate; aPTT, activated partial thromboplastin time; PT, prothrombin time.

Common point-of-care tests of coagulation

Point-of-care (POC) testing, or testing at the bedside, has become more frequently used in the perioperative period due to the technologic advancement and miniaturization of monitoring devices. The benefits of POC tests, compared with conventional laboratory-based tests, include faster turnaround times and the ability to assess the coagulation status of whole blood. POC monitors that are currently available can be used to measure the ability of blood to generate clot, heparin concentrations, the viscoelastic properties of whole blood, and platelet function.

Functional measures of coagulation

Activated clotting time

The activated clotting time (ACT) measures the adequacy of the intrinsic and common pathways. Fresh whole blood is added to a contact activation initiator, such as celite or kaolin, that initiates and accelerates clot formation, and the time to clot formation is measured. Two commercial ACT monitors currently in use, the Hemochron (International Technidyne, Inc., Edison, NJ) and the Hepcon and ACT II (Medtronic Blood Management, Parker, CO) automate clot detection by different mechanisms.

Clinically, the ACT is commonly used in the operating room to monitor heparin therapy. Advantages of the ACT are its low cost, simplicity of use, speed, and linear response even at high heparin concentrations. However, the utility of the ACT is affected by poor reproducibility of results and low sensitivity to low heparin concentrations. Factors that can prolong the ACT are hypothermia, hemodilution, thrombocytopenia, and platelet dysfunction.

Heparin concentration measurement

The most common method for assessing heparin concentration in the perioperative period is protamine titration. Protamine titration is capable of measuring heparin concentrations due to the fact that every 1 mg of protamine will inhibit approximately 100 units of heparin (1 mg). Thus, if a blood sample is divided and analyzed with several doses of protamine, the portion with the closest heparin and protamine concentrations will clot most rapidly. The appropriate heparin dose to obtain a specific plasma heparin concentration can be determined, as well as the amount of protamine needed to reverse a specific heparin concentration. Advantages of the protamine titration method include relative resistance to the effects of hypothermia and hemodilution, as well as sensitivity at low heparin concentrations. POC monitors currently in use, such as Hepcon HMS (Medtronic Blood Management), use automated measurement techniques.

Viscoelastic measures of coagulation

Thromboelastography and the sonoclot

The thromboelastograph (TEG) (Haemascope, Niles, IL), like other viscoelastic measures of coagulation, is capable of measuring the complete coagulation process, from initial fibrin formation through fibrinolysis. The changes in viscoelasticity at all stages are both measured and displayed graphically. Even though the various TEG parameters do not directly correlate with other laboratory-based coagulation tests, they do correlate with specific abnormalities throughout the coagulation process. Figure 147-2 displays the variables measured by the TEG, as well as common abnormalities. Although the TEG is occasionally used in cardiac and trauma surgery, it is most frequently utilized during liver transplantation. The amounts of packed red blood cells and fresh frozen plasma that are transfused are lower when the TEG is used to guide transfusion, compared with transfusing based on routine coagulation tests.

The Sonoclot Analyzer (Sienco, Inc., Arvada, CO) is another device used to monitor the viscoelastic properties of blood. It provides information on the entire hemostatic process in both a qualitative and quantitative fashion. The qualitative graph is known as the Sonoclot Signature (Figure 147-3), and the quantitative results measured are the ACT, the clot rate, and platelet function.

Platelet function monitors

Optical platelet aggregometry is considered by many to be the reference standard for platelet function monitoring, although the method suffers from a lack of standardization, as well as the cost of the test itself and the amount of labor required to perform the test. As mentioned previously, viscoelastic coagulation tests (TEG and Sonoclot) reflect platelet dysfunction, but without significant modification (such as the platelet mapping [Haemascope] paradigm), they have limited sensitivity and specificity. Several platelet function monitors have recently been marketed as POC devices, including the PFA-100 (Platelet Function Analyzer; Dade International Inc., Miami, FL) and Plateletworks (Helena Laboratories, Beaumont, TX). The PFA-100 simulates injury via a membrane with an aperture that contains platelet activators (adenosine diphosphate or epinephrine) and has been shown to be capable of identifying congenital and acquired platelet dysfunction. Plateletworks measures the percentage of aggregation of platelets in the presence and absence of collagen or adenosine diphosphate and correlates with optical platelet aggregometry. Unfortunately, there remains a remarkable variability of results when all of these methods are compared.