[0001] This PCT international application claims benefit of U.S. Patent Application Serial No. 62/188,254 filed on 2 July 2015 in the U. S. Patent and Trademark Office.

BACKGROUND

[0002] The present invention is in the field of systems, methods, and computer program products for analyzing results of a blood sample test to produce diagnoses and treatment recommendations .

[0003] Coagulation disorders contribute significantly to the morbidity and mortality of trauma patients. Thromboelastography (TEG) is a method of testing the efficiency of blood coagulation. Analysis of TEG results is typically performed by a trained operator. TEG analysis is not being widely applied because it requires specific training in the interpretation of its results.

[0004] In at least one embodiment, the automated system described herein removes that barrier by presenting the results of TEG analysis in a simplified format to practitioners who would normally not consider using this tool due to lack of training. By achieving this, the benefits of TEG will potentially become available to a larger patient population.

SUMMARY OF THE INVENTION

[0005] An embodiment of the invention provides a system and method for analyzing results of a blood sample test to produce diagnoses and treatment recommendations. The system can include a first processor that determines whether a hemostatic function of a patient is normal or abnormal. When the hemostatic function is abnormal the first processor determines whether the body temperature of the patient is below normal, determines whether the blood pH of the patient is below normal, tests for the presence of heparin in the patient's blood, and/or diagnoses the patient with delayed clot, wherein the delayed clot is due to low coagulation factors in the patient's blood. A second processor determines whether the patient's alpha angles are abnormal. When the patient's alpha angles are abnormal the second processor diagnoses the patient with slow clot, wherein the slow clot is due to low fibrinogen in the patient's blood, and/or administers cryoprecipitate to the patient.

[0006] A third processor determines whether the patient's MA measurements are normal or abnormal. When the patient's MA measurements are abnormal the third processor diagnoses the patient with weak clot, wherein the weak clot is due to at least one of the patient's low platelet count and the patient's platelet dysfunction, and/or administers platelets. A fourth processor determines whether the patient's LY30 measurement is normal or abnormal. When the patient's LY30 measurement is abnormal the fourth processor diagnoses the patient with hyperfibrinolysis, wherein the hyperfibrinolysis causes the patient's clot to break down in an actual amount of time that is less than an expected amount of time, and/or administers tranexamic acid to the patient.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0007] The present invention is described with reference to the accompanying drawings. In the drawings, like reference numbers indicate identical or functionally similar elements.

[0008] FIG. 1 is a flow diagram illustrating a method for analyzing results of a blood sample test to produce diagnoses and treatment recommendations according to an embodiment of the invention;

[0009] FIG. 2 is a diagram illustrating a system for analyzing results of a blood sample test to produce diagnoses and treatment recommendations according to an embodiment of the invention; and

[0010] FIG. 3 is a diagram illustrating a computer program product according to an embodiment of the invention.

DETAILED DESCRIPTION

[0011] Exemplary, non-limiting, embodiments of the present invention are discussed in detail below. While specific configurations are discussed to provide a clear understanding, it should be understood that the disclosed configurations are provided for illustration purposes only. A person of ordinary skill in the art will recognize that other configurations may be used without departing from the spirit and scope of the invention.

[0012] At least one embodiment of the invention provides an automated system that interprets the results generated by a thromboelastograph and produces a set of diagnoses and recommendations to treat a patient. The system can connect through a computer port to a thromboelastography (TEG) device from which the system collects blood-sample readings. As the data is collected, the system can plot the values read from the TEG device on a computer screen while simultaneously providing an analysis and treatment options to the system operator based on the values. Thus, the system can perform complex processing of multiple TEG parameters without human interaction that cannot be performed in the human mind or using pen and paper.

[0013] In order to provide analysis of the TEG readings, the system can process multiple TEG parameters, such as, for example, R (which describes the rate of thrombin generation) and MA (which represents the degree of platelet and fibrinogen effectiveness). The TEG parameters can be processed to quantitatively assess a patient's level of coagulation status. The TEG parameters can be analyzed to establish whether the patient's blood is in a hypocoagulable, fibrinolytic, or hypercoagulable state. In at least one embodiment, the analysis is constantly performed as the TEG plot develops, and the results are presented as a diagnosis to the system operator along with the TEG plot on a computer screen.

[0014] Based on the diagnosis generated, the system can also produce treatment options, such as, for example, the administration of cryoprecipitate, platelet concentrate, fresh frozen plasma (FFP), or tranexamic acid, among others, using, for example, the US Army Institute of Surgical Research's Joint Trauma System Clinical Practice Guideline for Damage Control Resuscitation. In at least one embodiment, these recommendations are presented in a simplified language to the system operator, as well as recommended blood products and/or drugs for administering to the patient.

[0015] The use of TEG analysis may improve the outcome of trauma patients by allowing clinicians to provide effective treatments for each individual case, avoiding unnecessary procedures that could result in further complications. Aside from the guidance the system can provide to clinicians for the treatment of patients, the system can also be used as a training aid for practitioners who have not been formally taught on the usage of thromboelastography. The system can also incorporate results of other laboratory tests or data from other monitoring systems to provide additional sets of diagnoses and treatments. Moreover, the system can be incorporated as a module into larger decision support systems. The system can provide for the electronic implementation of rules for determining the blood coagulation status of a patient. Rules can also be implemented to determine possible treatment options based on a given blood coagulation status.

[0016] As described below, the system can provide decision support capability to TEG devices for non-expert providers. In order to achieve this, the system can extract one or more "TEG parameters" from the graph produced by a TEG device for a blood sample. The system can then analyze these parameters and determine the blood coagulation status of the sample, as well as possible treatment options for the patient. All of the results can be presented to the system operator in plain language as diagnoses and treatment recommendations on a computer screen.

[0017] The system could be used by medical care providers who do not have previous experience or training with this technology. Less experienced personnel may be able to run the system and with proper supervision and training could also respond to the treatment options given by the system. Beyond a laboratory hospital setting, the system could also be used in pre-hospital environments. [0018] The system can be incorporated into the two main thromboelastography-based blood coagulation analyzers currently available in the market: the TEG5000 by Haemonetics, Inc., and the ROTEM by Tern Innovations GmbH. In addition, the system can be deployed as a standalone unit to process TEG readings from blood coagulation tests previously performed.

[0019] FIG. 1 is a flow diagram illustrating a method for analyzing results of a blood sample test (e.g., a test performed with a thromboelastography device) to produce diagnoses and treatment recommendations according to an embodiment of the invention. It is determined whether a hemostatic function of a patient is normal or abnormal 110. As used herein, the terms "determine", "determined", and "determining" include measure, measured, measuring, quantify, quantified, quantifying, identify, identified, identifying, estimate, estimated, estimating, calculate, calculated, calculating, compute, computed, computing, and the like.

[0020] The hemostatic function of the patient can be determined by the kinetics of the clot formation, the clot strength, and/or the clot lysis (i.e., break down of the clot). The kinetics of clot formation, clot strength, and/or clot lysis can be determined by estimating the patient's thrombin generation and/or platelet generation, wherein thrombin generation can be inferred by taking the first derivative of the TEG curve. A hemostatic function below a first threshold or above a second threshold is abnormal; and a hemostatic function between the first and second thresholds is normal. An embodiment of the invention allows administrator users (e.g., treating physician, unit medical director) to set individual threshold parameters for all values used by the algorithm to determine diagnosis and treatment recommendations.

[0021] When the hemostatic function is abnormal, it is determined whether the body temperature of the patient is below normal (e.g., 37 degrees Celsius) and/or whether the blood pH of the patient is below normal (e.g., within 7.35 and 7.45) 120. In at least one embodiment, when the hemostatic function is abnormal, the patient's blood is tested for the presence of heparin and/or the patient is diagnosed with delayed clot 120. The delayed clot may be due to low coagulation factors in the patient's blood, wherein the coagulation factors can include plasma and platelet-bound proteins that comprise a coagulation system and the coagulation system's regulators. The plasma and platelet-bound proteins can include Factors II, V, VII, VIII, IX, X, XI, XII, XIII, Protein C, Protein S, TFPI, TAFI, plasminogen, tissue plasminogen activator, alpha-2 antiplasmin, and/or antithrombin.

[0022] It is determined whether the patient's alpha levels are normal or abnormal 130. Alpha levels (also referred to herein as the alpha angle) can represent fibrinogen levels in the patient's blood, wherein the alpha angle can be used as an estimate of the rate of fibrin polymerization. In at least one embodiment, abnormal alpha levels are below 52 degrees and above 73 degrees; and, normal alpha levels are between 52 degrees and 73 degrees. In at least one embodiment of the invention, when the patient's alpha levels are abnormal, the patient is diagnosed with slow clot and/or cryoprecipitate is administered to the patient 140. As used herein, the term "administered" (or "administer") can include sending a signal to an external device, the signal including instructions to dispense a drug to a patient. The slow clot may be due to low fibrinogen in the patient's blood. Other factors that can affect slow clot include thrombin generation, platelet number, and/or hemostatic function.

[0023] It is determined whether the patient's MA measurements are normal or abnormal 150. In at least one embodiment, MA measurements represent a degree of platelet and fibrinogen effectiveness, wherein abnormal MA measurements are below 41.8 mm and above 63.0 mm, and wherein normal MA measurements are between 41.8 mm and 63.0 mm. In at least one embodiment of the invention, when the patient's MA measurements are abnormal, the patient is diagnosed with weak clot and/or platelets are administered to the patient 160. The weak clot may be due to the patient's low platelet count and/or the patient's platelet dysfunction.

[0024] It is determined whether the patient's LY30 levels are normal or abnormal 170. In at least one embodiment, LY30 levels represent a rate of fibrinolysis, wherein normal LY30 levels are less than 7%, and wherein abnormal LY30 levels are 7% or greater. The range for normal LY30 levels, normal body temperature, normal blood pH, normal alpha levels, and/or normal MA measurements can be defined by the system administrator. In at least one embodiment of the invention, when the patient's LY30 levels are abnormal, the patient is diagnosed with hyperfibrinolysis and/or tranexamic acid is administered to the patient 180. The hyperfibrinolysis can cause the patient's clot to break down faster than normal, i.e., in an actual amount of time that is less than an expected amount of time. Normal percentage clot breakdown at 30 minutes of run time (LY30) is 0-2%. In the setting of trauma, anything more than this can be considered abnormal. In other non-trauma settings, a higher threshold for lysis might be acceptable.

[0025] FIG. 2 is a diagram illustrating a system 200 including hardware components

210, 220, 230, and 240 according to an embodiment of the invention. More specifically, the system 200 analyzing results of a blood sample test (e.g., a test performed with a

thromboelastography device) to produce diagnoses and treatment recommendations, wherein a first processor that determines whether a hemostatic function of a patient is normal or abnormal. As used herein, the term "processor" includes a microprocessor, a CPU, and a computer hardware component. In at least one embodiment, the steps performed by the hardware components 210, 220, 230, and 240 are performed by a single processor.

[0026] When the hemostatic function is abnormal the first processor determines whether the body temperature of the patient is below normal (e.g., 37 degrees Celsius), determines whether the blood pH of the patient is below normal (e.g., 7.35 and 7.45), tests for the presence of heparin in the patient's blood, and/or diagnoses the patient with delayed clot. The delayed clot can be due to low coagulation factors in the patient's blood, wherein the coagulation factors can include Factors II, V, VII, VIII, IX, X, XI, XII, XIII, Protein C, Protein S, TFPI, TAFI, plasminogen, tissue plasminogen activator, alpha-2 antiplasmin, and/or antithrombin.

[0027] The first processor determines the hemostatic function of the patient by the kinetics of clot formation, clot strength, and/or clot lysis. The first processor estimates the patient's thrombin generation and/or platelet generation to identify kinetics of clot formation, clot strength, and/or clot lysis. In at least one embodiment, a hemostatic function outside ranges and values determined by administrator users (e.g., treating physician, lab director) is supported by the system. Ranges for values can be set by a system administrator.

[0028] The second processor 220 determines whether the patient's alpha levels are abnormal. When the patient's alpha levels are abnormal the second processor diagnoses the patient with slow clot and/or administers cryoprecipitate to the patient. In at least one embodiment, the second processor sends a signal to an injection pump. As used herein, the term "administers", "administered", and "administering" includes providing a

recommendation to the user (e.g., treating physician, nurse, or other medical care staff) to administer a drug to a patient. The slow clot can be due to low fibrinogen in the patient's blood. In at least one embodiment, the alpha levels represent fibrinogen levels in the patient's blood, wherein normal alpha levels are between 52 degrees and 73 degrees.

[0029] The third processor 230 determines whether the patient's MA measurements are normal or abnormal. When the patient's MA measurements are abnormal the third processor diagnoses the patient with weak clot and/or administers platelets. The weak clot may be due to the patient's low platelet count and/or the patient's platelet dysfunction. In at least one embodiment, the MA measurements represent a degree of platelet and fibrinogen

effectiveness, wherein normal MA measurements are 41.8 mm and 63.0 mm.

[0030] The fourth processor 240 determines whether the patient's LY30 levels are normal or abnormal. When the patient's LY30 levels are abnormal the fourth processor diagnoses the patient with hyperfibrinolysis and/or administers tranexamic acid to the patient. In at least one embodiment, the first processor 210, second processor 220, third processor 230, and fourth processor 240 are a single processor. The hyperfibrinolysis can cause the patient's clot to break down in an actual amount of time that is less than an expected amount of time. In at least one embodiment, the LY30 levels represent the rate of fibrinolysis, wherein normal LY30 levels are less than 7%. Fibrinolysis is a normal body process that prevents blood clots that occur naturally from growing and causing problems. The ranges of normal LY30 levels, normal body temperature, normal blood pH, normal alpha levels, and/or normal MA measurements can be defined by the system administrator.

[0031] As will be appreciated by one skilled in the art, aspects of the present invention may be embodied as a system, method or computer program product. Accordingly, aspects of the present invention may take the form of an entirely hardware embodiment or an embodiment combining software and hardware aspects that may all generally be referred to herein as a "circuit," "module" or "system." Furthermore, aspects of the present invention may take the form of a computer program product embodied in at least one computer readable medium having computer readable program code embodied thereon.

[0032] Any combination of at least one computer readable medium may be utilized. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having at least one wire, portable computer diskette, hard disk, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or Flash memory), optical fiber, portable compact disc read-only memory (CD-ROM), optical storage device, magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.

[0033] A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0034] Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.

[0035] Computer program code for carrying out operations for aspects of the present invention may be written in any combination of at least one programming languages, including an object oriented programming language such as Java, Smalltalk, C++, Objective C or the like and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).

[0036] Aspects of the present invention are described below with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute with the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.

[0037] These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function/act specified in the flowchart and/or block diagram block or blocks.

[0038] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.

[0039] Referring now to FIG. 3, a representative hardware environment for practicing at least one embodiment of the invention is depicted. This schematic drawing illustrates a hardware configuration of an information handling/computer system in accordance with at least one embodiment of the invention. The system comprises at least one processor or central processing unit (CPU) 510. The CPUs 510 are interconnected with system bus 512 to various devices such as a random access memory (RAM) 514, read-only memory (ROM) 516, and an input/output (I/O) adapter 518. The I/O adapter 518 can connect to peripheral devices, such as disk units 511 and tape drives 513, or other program storage devices that are readable by the system. The system can read the inventive instructions on the program storage devices and follow these instructions to execute the methodology of at least one embodiment of the invention. The system further includes a user interface adapter 519 that connects a keyboard 515, mouse 517, speaker 524, microphone 522, and/or other user interface devices such as a touch screen device (not shown) to the bus 512 to gather user input. Additionally, a communication adapter 520 connects the bus 512 to a data processing network 525, and a display adapter 521 connects the bus 512 to a display device 523 which may be embodied as an output device such as a monitor, printer, or transmitter, for example.

[0040] The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises at least one executable instruction for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.

[0041] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the root terms "include" and/or "have", when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of at least one other feature, integer, step, operation, element, component, and/or groups thereof.

[0042] The corresponding structures, materials, acts, and equivalents of all means plus function elements in the claims below are intended to include any structure, or material, for performing the function in combination with other claimed elements as specifically claimed. The description of the present invention has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the invention. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.

INDUSTRIAL APPLICABILITY

[0043] A system featuring methods of analyzing results of a blood sample test to produce diagnoses and treatment recommendations. The provided systems and methods are particularly suited for determining whether a hemostatic function of a patient is abnormal, whether the patient's alpha angles are abnormal, whether the patient's MA measurements are abnormal, and whether the patient's LY30 measurement is abnormal.