Sienco®, Inc. - Sonoclot® Overview

Sonoclot Coagulation & Platelet Function Analyzer
An Overview

For In Vitro Diagnostic Use

Introduction

The Sonoclot Analyzer Overview describes benefits and features, principle of operation and clinical applications of the Sonoclot^® Coagulation & Platelet Function Analyzer ("Sonoclot Analyzer"). We will demonstrate why the Sonoclot Analyzer offers clinicians a unique method of testing that can simplify diagnosis of numerous coagulopathies and speed therapeutic management. The Sonoclot whole blood analysis is unlike other coagulation tests which either suffer from the lack of cellular elements or only provide data on separate components of the blood, thereby overlooking important interactions essential to the clinical evaluation of hemostasis. The Sonoclot Analyzer rapidly provides accurate information on the entire hemostasis process including coagulation, fibrin gel formation, clot retraction (platelet function) and fibrinolysis. The Sonoclot Analyzer generates both a qualitative graph, known as the Sonoclot Signature, and quantitative results on the clot formation time (Activated Clotting Time - Onset) and the rate of fibrin polymerization (Clot RATE) for identifying numerous coagulopathies including platelet dysfunction, factor deficiencies, anticoagulant effect, hypercoagulable tendencies and hyperfibrinolysis. The Sonoclot Analyzer is a reliable and simple to use instrument which can be utilized in operating rooms, coagulation labs, STAT labs and intensive care units. The Sonoclot Analyzer can provide numerous benefits including:

Improved hemostasis management in surgery
Reduced usage of donor blood products
Faster identification of mechanical versus hemostatic bleeders
Accurate and inexpensive heparin anticoagulation management
Quick and easy screening for hypercoagulable patients

Healthcare professionals are pursuing a balance between quality of care and cost containment. Sienco is dedicated to helping you meet this challenge through cost-effective products of superior quality and reliability. In the prevailing hospital economic climate, the ability to provide cost savings while improving patient care will be a powerful incentive for Sienco's Sonoclot Analyzer and related tests.

Principle of Operation

The detection mechanism within the Sonoclot Analyzer responds to mechanical changes that occur within the blood sample. This mechanism consists of a tubular probe that oscillates up and down within a blood sample. The electronic drive and detection circuitry senses the resistance to motion that the probe encounters from the blood sample and generates an analog electronic signal. The resulting electronic signal is processed by a microcomputer within the Analyzer and reported as the Clot Signal.

As the blood sample clots, numerous mechanical changes related to the performance of the patient's hemostasis system occur that alter the Clot Signal value. The record of the clot evolution is saved as a graph of the Clot Signal value versus time and printed on a thermal graphics printer. This graph is called the Sonoclot Signature. A typical Sonoclot Signature is shown to the left.

Sonoclot Analyzer and Hemostasis

The sample Sonoclot Signatures^TM shown throughout this overview were run with Sienco's celite activated SonACT^TM test, Part Number 800-0432.

Coagulation

In a Sonoclot Signature the coagulation cascade reactions develop from the beginning of the Signature and continue throughout the liquid phase. The liquid phase ends when the viscosity of the sample begins to increase with thrombin generation and the resulting initial fibrin formation. The time that the test in the Sonoclot Signature remains a liquid is reported as the Onset. This time is the endpoint for coagulation cascade tests.

Fibrin Gel Formation

Once thrombin forms in the test sample, the fibrinogen converts to fibrin monomers. The fibrin monomers spontaneously polymerize into a fibrin gel. Gel formation is effected by both the rate of the fibrinogen to fibrin conversion and the amount of fibrinogen. The fibrin gel formation is characterized with the slope of the Sonoclot Signature during the gel formation (Clot RATE) and by the height of the Signature when gel formation is completed. This information is important in several clinical applications including identifying hypercoagulable screening, anticoagulant management and fibrin hemodilution.

Clot Retraction (Platelet Function)

Clot retraction occurs when platelets function properly. In a Sonoclot Analysis platelets will retract the fibrin gel. One very valuable feature of the Sonoclot Analyzer is its ability to capture the clot retraction that functioning platelets perform on a fibrin clot. The photograph to the left shows the role of platelets in retracting a clot. The dark lines are strands of fibrin. These fibrin strands link together into a gel. The platelets adhere to multiple nodes of the fibrin gel and cause the gel to collapse together or retract.

The Sonoclot Signature responds to the clot retraction occurring within the test sample. As the clot retracts it tightens causing the Sonoclot Signature to rise. Eventually, the clot will often pull away from some of the surfaces of the cuvette or probe. The Sonoclot Signature falls when the clot pulls away from the inner surface of the cuvette or probe.

Clot retraction is measured by both the time it takes for retraction to occur and the degree of retraction. One useful measurement to characterize clot retraction is the Time to Peak. Generally, the faster the time to peak the greater the platelet function. Also, a qualitative assessment of the clot retraction is useful. Sharp well defined peaks indicate strong retraction; dull or poorly defined peaks indicate weak retraction.

Hyperfibrinolysis

Eventually fibrin clots dissolve through activation of the fibrinolytic system. The activated enzyme plasmin is formed from plasminogen and breaks fibrin strands into smaller fibrin split products. The fibrin split products do not polymerize so as this lysing progresses, the fibrin gel dissolves.

With normal hemostasis the process of fibrinolysis occurs at much slower rates than coagulation, fibrin gel formation or clot retraction. For a normal sample lysis will occur only after many hours. Since most Sonoclot test runs do not extend beyond 45 to 60 minutes, lysis will be detected on a Sonoclot Signature when hyperfibrinolysis occurs. The Sonoclot Signature to the left captures hyperfibrinolysis.

Several important comments pertain to the identification of hyperfibrinolysis:

Coagulation and fibrin gel formation are not impaired by fibrinolytic activity.
Platelet function may be significantly reduced by fibrinolytic activity. Notice that the above Sonoclot Signature never develops the characteristic rise because the platelets have been inhibited by the plasmin and consequently do not tighten the fibrin gel.
As the fibrin gel dissolves the Clot Signal falls smoothly back to a value near and often slightly below the original liquid response.

Normal Values for Sonoclot Analyzer Tests

When interpreting a Sonoclot Signature, it is essential that the user know what test was run on the Sonoclot Analyzer and how the sample was collected. Different tests use different reagent quantities or formulations that dramatically affect how the clot forms during the Sonoclot Analysis. Different sample collection methods also greatly affect clot formation. Any of these possible variations alter the Sonoclot Signature and the corresponding test results. When you are interpreting a Sonoclot Signature, you are really interpreting a Sonoclot Signature of a blood sample collected in a specific manner and tested with a specific type of cuvette and reagent formula. Refer to the specific test being run for applicable normal ranges.

Hemostasis Monitoring in Surgery

Effects of Heparin on a Sonoclot Signature

Heparin inhibits the formation of thrombin by greatly multiplying the potency of the thrombin inhibitor, ATIII. Thrombin plays multiple roles in hemostasis including cleaving fibrinogen into fibrin monomer and stimulating platelets to aggregate. Because of the multifaceted role of thrombin and heparin's antithrombin effect (through ATIII), it isn't surprising that heparin has multiple effects on a Sonoclot Signature. At the right is a typical response to heparin tested with Sienco's celite activated SonACT test.


Before Heparin	Aefore Heparin

Three separate effects of heparin on the Sonoclot Signature are:

The sample remains a liquid longer (later Onset)
The gel formation occurs slower (lower Clot RATE)
Clot retraction is very slow or not observed (less platelet activity)

Patients respond to heparin differently. Some patients show heparin resistance by having less than normal response to heparin. The Clot RATE result is very useful in further quantifying the anticoagulant effect beyond just the Onset. The Clot RATE is an important hypercoagulable flag and should be maintained below 10 to 12 units per minute for cardiopulmonary bypass procedures to ensure effective anticoagulant management.

Rate of Gel Formation (Clot RATE) Under High Dose Heparin Anticoagulant Management

Slow (< 2)	Normal (2 - 8)	Fast (> 8)

Cardiovascular Surgery

Anticoagulant monitoring in cardiovascular surgery involves running a baseline blood analysis to screen for potential coagulopathies, running additional ACT tests to determine the adequacy of anticoagulant effect while the patient is on heparin, and running a post protamine ACT to identify any hemostasis deficiencies.

Cardiovascular Surgery Example #1 - Typical Case

Cardiovascular surgery subjects the hemostatic system to multiple stresses from intraoperative bleeding, anticoagulant treatment, red blood cell washing, and physical trauma. To best understand and manage an individual's hemostatic system, always run a baseline for the patient as early into the case as is convenient, but always prior to anticoagulant intervention.

These Signatures are from a typical cardiovascular surgery case that did not experience excessive bleeding. The first Signature identifies a strong hemostatic system. The time for initial fibrin formation was normal (Onset = 137 seconds), the fibrin formation was normal (Clot RATE = 26 units per minute), and the clot retraction was both fast and strong (Time to Peak = 6 minutes).

The next two Signatures were taken while the patient was anticoagulated with heparin. Notice in the Signature just to the right that the patient showed a normal response to heparin; the Onset extended from 137 to 746 seconds, and the Clot RATE attenuated from 26 to 4.8 units per minute. Later while still anticoagulated, the Signature shows the effects of heparin have slightly diminished, but the patient is still well anticoagulated. The Onset of 586 seconds and Clot RATE of 7.9 units per minute confirm adequate anticoagulation.

After heparin reversal, the Sonoclot Signature records a normal hemostatic profile. The clot begins to form in a normal amount of time (Onset = 123 seconds); the fibrin polymerization is normal (Clot RATE = 20 units per minute), and the clot retraction of the fibrin gel is normal (Time to Peak = 11.5 minutes). The Signature shows no hemostatic deficiencies.

It is useful to compare the baseline Signature with the post bypass Signature. In this patient below, when these Signatures are compared, you can observe some reduction in the strength of the fibrin gel. Look at the height of the Signature after gel formation. In the baseline Signature the Clot Signal value is about 50 Clot Signal units (4.5 minutes into the Signature) when the fibrin formation nears completion. This Clot Signal value in the post bypass Signature has reduced slightly to a value of about 45 Clot Signal units (6 minutes into the Signature). The degradation in clot retraction (platelet function) is more pronounced. The baseline Time to Peak was 6 minutes and the post bypass Time to Peak extended to 11.5 minutes. Some degradation in hemostatic performance should be expected after cardiovascular surgery.


Baseline		Post Pump

Cardiovascular Surgery Example #2 - Platelet Dysfunction

Platelet dysfunction is often a major factor in excessive bleeding in cardiovascular surgery. The platelet dysfunction may be present prior to surgery or it may develop during the procedure.

This case example begins with the baseline Signature at the left. Hemostasis is normal; the liquid phase (clotting factors), gel formation (primarily fibrin), and clot retraction (platelet function) are normal. Post protamine the Signature has changed dramatically from the baseline Signature. Although the liquid phase and gel formation are normal, clot retraction is nearly absent. A patient with a post protamine Signature lacking significant clot retraction is a likely candidate for oozing and increased post operative bleeding. Quick identification of a platelet dysfunction and proper intervention can help reduce post operative bleeding and possible additional coagulopathies associated with blood loss.


Baseline		Post Pump

Cardiovascular Surgery Example #3 - Identification of a Mechanical Bleeder

A cardiovascular surgery patient was experiencing excessive post operative bleeding. The Sonoclot Signature taken in the intensive care unit is shown. This blood remained a liquid for 141 seconds so there are sufficient clotting factors to begin clot formation in a normal manner. The Clot RATE is 23 which indicates a normal rate of fibrin polymerization. The clot retraction is somewhat slow and the Peak is poorly defined, indicating slightly below normal platelet function.

The initial step to control the post operative bleeding was to build up the hemostatic system. A shotgun approach was attempted by administering routine quantities of cryoprecipitate, platelets, DDAVP, fresh frozen plasma and 50 mg protamine. The effect of this intervention on the Sonoclot Signature is shown to the left. This Sonoclot Signature showed strong hemostasis performance from coagulation through gel formation and clot retraction. However, the post operative bleeding was not corrected until this patient was taken back to the operating room. This illustrates one use of the Sonoclot Analyzer in differentiating hemostatic bleeders from mechanical bleeders.

Cardiovascular Surgery Example #4 - Hyperfibrinolysis

Hyperfibrinolysis is not common in cardiovascular surgery, but when it occurs, quick identification with proper intervention can help avoid a severe bleeding complication. This Signature was run after heparin reversal. The Signature shows the classic hyperfibrinolysis indicator of the Clot Signal returning to a value at or below the initial Clot Signal value during the liquid phase. A clot formed and then it dissolved back into a liquid.

This patient was given Amicar to treat the hyperfibrinolysis. The result on the Sonoclot Signature substantiates that the hyperfibrinolysis has been reduced. Several points related to hyperfibrinolysis management should be understood. Plasmin is the active enzyme that dissolves fibrin. Plasmin is formed when the fibrinolytic system is activated. The trauma of cardiovascular surgery activates the fibrinolytic system. The common approach to treat hyperfibrinolysis is to inhibit or remove plasmin. Amicar is the most common antifibrinolytic drug. It inhibits the formation of plasmin but does not remove plasmin that has already formed. Consequently, Amicar will not produce immediate results. The response to Amicar depends on the patient's ability to remove the circulating plasmin.

Aprotinin is another antifibrinolytic drug. It acts directly on plasmin and inhibits circulating plasmin. It can have a rapid effect on reversing hyperfibrinolysis. Plasmin also inhibits platelets. Sometimes a Sonoclot Signature will capture improved platelet function after aprotinin or Amicar treatment if poor clot retraction is the result of plasmin inhibited platelets.

Liver Transplant Example

The Sonoclot Analyzer is used in liver surgery. In these cases severe coagulopathies are much more frequent than in most other procedures. During the liver transplant procedure ten Signatures were collected. For convenience the progression of hemostasis changes are summarized using only three of the Signatures. The baseline Signature at the left shows a slightly prolonged liquid phase with an Onset of 162 seconds and normal gel formation with a Clot RATE of 39. However, the Signature does not contain any clot retraction. After the blood formed a gel, it remained a gel without any clot retraction (no platelet function). Platelet dysfunction is common with liver disease.

During the surgery the Signature shows classic hyperfibrinolysis. The sample formed a gel and the gel dissolved back into a liquid. The Signature does not show any indication of clot retraction.

This third Signature was run after the new liver had been functioning within the patient for sufficient time to reduce hyperfibrinolysis. Notice that the Signature contains the normal components of hemostasis. The clot begins to form after a normal time delay. The fibrin gel forms normally. Clot retraction is now apparent in the Signature although still prolonged.

Conclusion

Sienco's Sonoclot Coagulation & Platelet Function Analyzer provides useful information on multiple aspects of hemostasis. Standard coagulation testing results from a whole blood sample are available within minutes. Additional useful information regarding fibrin gel formation, clot retraction or platelet function, and fibrinolysis is also captured on the Sonoclot Signature. Clinical users are applying the Sonoclot Analyzer to a wide range of clinical and research applications throughout the world. Cardiovascular surgery is the primary use of the Sonoclot Analyzer because of the need for effective anticoagulant management, rapid identification of bleeding coagulopathies, and improved management of donor blood products. Sonoclot Analyzers are also in use in liver transplant surgery, obstetrics, coagulation labs, hypercoagulable screening, and trauma applications. If you have further questions or possible interest in an onsite evaluation, please contact Sienco.

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This page was last modified on 10/26/07
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