WO2019200436A1

WO2019200436A1 - System and method for inhibiting blood coagulation

Info

Publication number: WO2019200436A1
Application number: PCT/AU2019/050350
Authority: WO
Inventors: Gregory James Roger; Davor SARAVANJA
Original assignee: Spinal Developments Pty Ltd
Priority date: 2018-04-18
Filing date: 2019-04-18
Publication date: 2019-10-24

Abstract

Disclosed are methods and systems of inhibiting blood coagulation in a patient that includes reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the patient. A system for monitoring blood temperature is also disclosed.

Description

SYSTEM AND METHOD FOR INHIBITING BLOOD COAGULATION

TECHNICAL FIELD

This disclosure relates to a system and method for inhibiting blood coagulation in a patient and to blood temperature monitoring. The disclosure has particular application to inhibiting blood coagulation to reduce the risk of Deep Vein Thrombosis (DVT) and the disclosure is herein disclosed in that context.

However, it is to be appreciated that the disclosure has broader application and is not limited to that use and, for example, may be used for reducing the risk of coagulation in the body following surgery or following a thrombotic event, such as a stroke.

BACKGROUND ART

The prevention of deep venous thrombosis (DVTs) is a key aspect of patient management, particularly in the post-operative phase. DVTs typically form in the deep venous plexus of the calf and then extend into the thigh and more proximal, although they can arise in any vascular system given the right conditions.

However, clinically, the greatest area of concern are clots starting in the calf and extending through the lower limbs.

Treatments used to date include anti-coagulant drugs, sequential compression devices, early ambulation and devices to move the feet which cause the venous plexuses to be constricted“pumping” the blood through the vascular system. Normal ambulation achieves this effect and is how we assist our hearts in moving blood up against the column of blood pressing down. However, despite these methods there are ongoing concerns, and a continued rate of formation of deep venous thromboses. Anticoagulation can have somatic side effects and consequences and is contra-indicated in many types of surgery in the immediate post-operative period of one to two weeks. Early ambulation may also not be an option in many types of surgery. Finally, despite the use of these methods, often in combination, DVTs remain a significant clinical challenge and many times a cause of death or significant disability.

It is to be understood that, if any prior art is referred to herein, such reference does not constitute an admission that the prior art forms a part of the common general knowledge in the art, in Australia or any other country.

SUMMARY

Disclosed is a method of inhibiting blood coagulation in a patient including reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the patient, wherein the cooling of the blood temperature is controlled to remain localised to the first region.

A lowered blood temperature has deleterious effects on the coagulation system of the body, chiefly by inhibiting the enzymes required to“cascade” to form a clot of platelets and other blood components. The required drop in temperature is relatively modest. By 32 to 34 degrees Celsius, the functioning of platelets and associated coagulation factors has significantly decreased. Towards 25 degrees Celsius the coagulation function has been greatly compromised.

In a particular form, the present disclosure is directed towards lowering the temperature of a region of a patient, such as for example, the calf muscles and lower limbs, while leaving the rest of the body unaffected. In this way, the coagulation factors for blood, especially slow moving blood which is at greatest risk of clotting, will be altered sufficiently in the area of lowered temperature to reduce the risk of DVT forming.

The method may also include monitoring at least one characteristic of a second region of the patient. The second region may be closer to a core of the patient than the first region. In some forms, the method includes monitoring the patient and taking corrective action if the cooling of the region is not remaining sufficiently localised such that it could adversely affect the patient. Core temperatures of only a few degrees below normal are associated with a number of seriously undesirable

consequences, up to and including cardiac arrest. Core temperatures below 36 degrees are considered“hypothermic” and warranting intervention.

Also disclosed is a method of reducing the risk of DVT occurring in a limb of a patient comprising reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the limb susceptible to DVT so as to reduce the propensity of the blood in the first region of the patient’s limbs to coagulate.

Also disclosed is a system for monitoring blood temperature in a region comprising one or more sensors for monitoring one or more characteristics of the patient at or near the surface of one or more regions on the patient; and a processor for establishing information indicative of the blood temperature of the vascular structures of the region, and optionally more superficial vessels and tissues as well from the one or more characteristics.

Also disclosed is a method of inhibiting blood coagulation in a region of a patient including reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the patient. The method may also include monitoring blood temperature in the region by monitoring one or more characteristics of the patient through at least one noninvasive or minimally invasive measurement; and a processor for establishing information indicative of the blood temperature of the vascular structures of the region from the one or more characteristics.

Also disclosed is a system for inhibiting blood coagulation in a region of a patient comprising: - a cooling device for reducing the blood temperature in the vascular structures of at least a first region of the patient; and

- a controller for controlling the cooling device in reducing the blood

temperature in the vascular structures of the first region and/ or restoring of the blood temperature in the vascular structures of a second region of the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will now be described by way of example only, with reference to the accompanying drawings in which: Fig. l is a schematic view of a system for inhibiting blood coagulation in a limb of a patient;

Fig. 2 is a representation of temperature changes in the deep venous structures in the limb using the system of Fig. 1;

Fig. 3 is a schematic view of a system for inhibiting blood coagulation in the head of a patient;

Fig. 4 is variation of the system of Fig. 3; and

Fig. 5 shows details of implantable devices for use in the systems of Fig. 3 and Fig. 4.

DETAILED DESCRIPTION In the following detailed description, reference is made to accompanying drawings which form a part of the detailed description. The illustrative embodiments described in the detailed description, depicted in the drawings and defined in the claims, are not intended to be limiting. Other embodiments may be utilised and other changes may be made without departing from the spirit or scope of the subject matter presented. It will be readily understood that the aspects of the present disclosure, as generally described herein and illustrated in the drawings can be arranged, substituted, combined, separated and designed in a wide variety of different configurations, all of which are contemplated in this disclosure.

In one form, the disclosure provides a method of inhibiting blood coagulation in a patient includes reducing the blood temperature below a first threshold in the vascular structures of a first region of the patient, wherein the cooling of the blood temperature is controlled to remain localised to the first region.

In some forms, the method confines the cooling of the blood temperature to the vicinity of the first region so as not to reduce the core body temperature to a level that would negatively impact on the patient.

The method may also include monitoring at least one characteristic of a second region of the patient. The monitoring may be for ensuring that the cooling of the first region is remaining localised so as not to reduce core body temperature to an undesirable level. The second region may be closer to a core of the patient than the first region.

In some forms, the method includes monitoring the patient and taking corrective action if the cooling of the first region is not remaining sufficiently localised. In particular forms, the method further includes increasing the blood temperature of the patient when the monitored characteristic at the second region falls outside at least one parameter. In some forms, this may occur by reducing the rate and/or extent of cooling of the blood in the first region.

In some forms, the method of increasing the blood temperature comprises applying heating to the surface of the patient. The heating may be applied to a proximal region that is closer to the core of the patient than the first region. In particular forms, the first region is in a limb of the patient. In one form, the first region is the lower leg and the blood temperature in the femoral artery is reduced to below the first threshold.

In some forms, the first threshold is established so as to reduce the propensity of the blood in the first region to coagulate. In some forms, the first threshold is at or below 36 degrees C, and preferably at or below 35 degrees C. In particular forms, the first threshold is at or below 34 degrees C, preferably between 31 and 34 degrees C.

In some forms, the first threshold is less than 34 degrees C and may be as low as 22 degrees C.

In some forms, the method further comprises providing a coagulation response of the patient’s blood to alterations in blood temperature. The first threshold may be established based on the patient’s coagulation response.

The assessment of the coagulation response may in some forms be done as a pre- intervention procedure. The coagulation response may be assessed by reducing the blood temperature to a target temperature and measuring the INR

(international normalised ratio), aPTT (activated partial thromboplastin time) and/ or PTT (partial thromboplastin time) at that temperature. A profile of the coagulation response may be obtained by measuring the blood response at a range of different temperatures.

In particular forms, the second region is a proximal region that is closer to the core of the patient than the first region.

In some forms, the monitored characteristic is the blood temperature in the vascular structures of the second region. In a particular form, the at least one parameter, being the blood temperature in the vascular structures of the second region, is below a second threshold temperature. As this second threshold is giving information of the blood temperature closer to the core, the second threshold temperature is above the first threshold

temperature. In some forms the second threshold temperature may be in the order of 36 degrees C or even higher.

In some forms where the second region is a proximal region of a limb, the monitored characteristic is the blood temperature in the femoral vein at the proximal region of the limb.

In some forms, the monitored characteristic is established from a noninvasive or minimally invasive measurement of the patient.

In some forms, information indicative of the blood temperature of the vascular structures at the first and/or second region is established from a noninvasive or minimally invasive measurement.

In some forms, the information indicative of the blood temperature is established from measuring the skin surface temperature. In one form the skin surface temperature is then correlated to the blood temperature in the deeper vascular structures using one or more characteristics of the patient. This correlation may be determined by a processor incorporating one or more algorithms that has the one or more patient characteristics as factors. In one form, the patient

characteristics includes any one or more of BMI, leg diameter, body mass, ethnicity, age, sex, cardiac output, blood pressure, skin pinch thickness.

In another form, the blood temperature is established from a measurement of blood viscosity, such as by using doppler ultrasound technique. In another form, muscle fasciculations is utilised as a measure of vascular temperature. The muscle fasciculations may be measured by surface reading electrodes. In yet another form, pulse oximetry may be used as a measure of reduced metabolism which in turn may be used a measure of reduced blood temperature.

In one form, multiple ones of the above modalities may be used to determine the blood temperature.

In some forms, the method further comprises applying compression to the region. The compression applied may be modulated with the reducing the blood temperature such that resultant blood temperature of the limb is maintained within a predetermined range.

In some forms, the method further comprises monitoring the resistance of region to temperature transfer to the blood within the deep vascular structures. The method may further comprises collecting data of a response of the limb whilst the blood temperature in the vascular structures of at least a first region of the limb is reduced.

The method in any form as described above, may be applied to reduces the risk of DVT in a limb. In a further aspect, there is disclosed a method of reducing the risk of DVT in a limb susceptible to DVT comprising reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the limb so as to reduce the propensity of the blood in the first region of the limb to coagulate. In one form, the method confines the cooling of the blood temperature to the vicinity of the limb so as not to reduce the core body temperature to a level that would negatively impact on the patient.

In one form, the method includes monitoring the patient and taking corrective action if the cooling of the limb is not remaining sufficiently localised.

In a further aspect, there is disclosed a system for monitoring blood temperature in a region comprising one or more sensors for monitoring one or more

characteristics of the patient at the surface of one or more regions on the patient; and a processor for establishing information indicative of the blood temperature of the vascular structures of the region from the one or more characteristics.

In a further aspect, where a lower limb is being cooled, the skin surface temperatures of a remote limb, for example the arm, may be monitored to determine the core temperature modulation that may occur through cooling of the lower limb.

Also disclosed is a method of inhibiting blood coagulation in a region of a patient including reducing the blood temperature below a first threshold in the deep vascular structures of at least a first region of the patient. The method may also include monitoring blood temperature in the region by monitoring one or more characteristics of the patient at the surface of the patient; and a processor for establishing information indicative of the blood temperature of the vascular structures of the region from the one or more characteristics.

In yet a further aspect, a system for inhibiting blood coagulation in a region of a patient comprising: a cooling device for reducing the blood temperature in the deep vascular structures of at least a first region; and a controller for controlling the cooling device in reducing the blood temperature in the vascular structures of the first region and / or restoring of the blood temperature in the vascular structures of a second region of the patient.

In one form this system, further comprises one or more sensors for monitoring one or more characteristics of the patient at the surface of one or more regions on the patient; and a processor for establishing information indicative of the blood temperature of the vascular structures of the region from the one or more characteristics. In one form, the one or more sensors is for monitoring the skin surface temperature of the limb at one or more regions on the limb. The system further comprises a processor for establishing information indicative of the blood temperature of the vascular structures of the limb from the surface monitoring. In a particular form, the controller is responsive to the information from the processor indicative of blood temperature. In yet further forms, the system may further comprise a heating device for restoring the blood temperature in vascular structures of the patient. In a particular arrangement, the controller is operative to control the heating device to restore the blood temperature in the vascular structures of a second region of the patient that is closer to a core of the patient.

In some forms of system according to any form described above, the cooling device and /or the one or more sensors is formed as part of a garment that is applied over the limb. In some forms, the cooling device and/or the heating device is implanted in the patient. In one form, the device may be implanted around the vessel to be cooled.

In some forms, the implanted device may have means to measure the blood temperature in the vascular structure. When applied to cooling of a limb, it may be expected that cooling of the limb such as a leg will lead to cooling of the core temperature, the methods and systems described above may be applied in a manner that utilises the counter- current circulation to minimize if not eliminate this effect. The arterial supply to the leg, the femoral artery, runs next to the venous drainage, the femoral vein, both contained and intimately opposed to each other in a fascial sheath. As a consequence, the cooling effect of the methods and systems described above which may leads to indirectly cooled blood in the femoral vein, serves to cool the blood arriving from the core in the femoral artery. By this same method, the cooled blood in the vein is thereby heated.

This“counter-current heating” is therefore able to trap the cooling effect in the lower limb. Depending on the amount of cooling to reach the required coagulation response in the cooled blood, this counter current effect may be inadequate and so methods and systems may monitor the relative temperatures (particularly the temperature of the returning blood) and, as required, can provide a heating cuff around the thigh or other suitable location to ensure normalcy of the body’s core temperature.

The ideal temperature to cool the lower limb may also be varied. The response of a patient’s coagulation factors to cooling is variable. Pre-intervention tests that test the coagulation response to reduce temperatures, such as the activity of the enzymes at a series of lower than normal temperatures, may be used. Through data analysis groups of patients and their biometric data can be collected and the testing profiles minimized. Likewise, various inherited and acquired

coagulopathies can be tested for and the treatment regime adjusted accordingly.

However, the principle remains that for each patient a preferred set temperature for the venous complex of the limb, particularly the calf, can be determined and with the systems and methods of the disclosure this temperature can be reliably applied, monitored and adjusted without affecting the patient’s core temperature. In effect, the patient will be anti-coagulated (by lowered temperature) in the deep veins of the calves and lower limbs alone.

Fig. 1 discloses an embodiment of a system 10 for patient management, particularly in the post-operative phase, for reducing the risk of DVT occurring in the lower limbs 102 of the patient 100 and utilising the principles as outlined above.

The system includes a garment 12, shown in the form of a multiple wraps (14, 16, 18), one wrap 14 applied over the lower leg (or legs) 104 of the patient 100, and two other wraps (16, 18) applied over the upper leg (or legs) 106. Whilst the illustrated form shows the garment as having multiple wraps, it is to be appreciated that the system may take other forms, such as a single wrap or other garment, or discrete functional elements (cool packs, sensors, heating bands and the like) applied directly to the patient.

Two of the wraps (14, 16) are arranged to cool the leg 102 and include an integrated cooling device (not shown) that may be in the form, for example, of fluid passages that allow a cooling medium to be pumped through the wrap, whereas the third wrap 18 includes a heating device (for example a heating coil) embedded into that wrap 18. It is to be appreciated that the wraps with the cooling and heating devices may be designed so that cooling or heating may be applied to specific areas of the wrap (and therefore to specific areas of the patient limb). This may occur through having multiple discrete fluid passages or coils or switching arrangements that control the flow through the wraps.

The wraps are arranged on the leg(s), such that the wraps with the cooling devices (14,16) are disposed on distal regions of the limb, whereas the wrap with the heating device 18, is disclosed on a proximal region of the limb. The wraps (14, 16, 18) also include sensors (generally given reference numeral 26) to monitor the patient’s skin surface temperature. Whilst these sensors may be located at only discrete locations on the wraps, in one form they are more widely dispersed so as to monitor the skin temperature along the leg(s) of the patient.

The cooling and heating device and sensors are connected to a controller 20, through appropriate means (such as tubing, wires, and/or wirelessly). The purpose of the controller is to regulate cooling and/or heating of the leg(s), to monitor skin temperatures, process that monitored data to generate information indicative of the blood temperature of the vascular structures in the leg (e.g. in the femoral artery and vein) and to store relevant data. The stored data may include patient data (e.g. information regarding any one or more of BMI, leg diameter, body mass, ethnicity, age, sex, cardiac output, blood pressure, skin pinch thickness,) coagulation response of the patient’s blood to alterations in blood temperature (possibly calculated from the patient data), setting parameters for the patient management (including temperature setpoints), and stored response data from the patient.

The illustrated controller 20 includes a processor 22 and memory 24. The processor 22 is arranged to process programme instructions and data. Memory 24 is arranged to store programme instructions and data also in a known manner. Processor 22 may constitute one or more processing means, such as integrated circuit processors. The memory 24 may comprise any known memory architecture and may include hard disk, IC memory (ROM, PROM, RAM, etc.), and other types of additional memory such as CD ROM, and any other type of memory.

The controller may be part of a computer system and may be implemented by any known type of computing hardware such as, for example, a PC, by a number of networked PCs if required to implement a system of this embodiment, by a “mainframe architecture” including a remote computer and user workstations connected to the remote computer, by a client-server architecture, including a client computer accessing a server computer over a network, or by any other computing architecture.

Parts of the system may be housed in the“cloud”. This embodiment of the is implemented by appropriate software providing instructions for operation of the computing system hardware to implement the system of the embodiment and implement the method of the embodiment.

Part of the system or the entire computer system may be portable, and may be implemented, for example, by a laptop or tablet computer, or other portable device.

The computing system need not be connected to a network if this is not required by the software or computer architecture.

Fig. 2 illustrates the operation of the system 10 by way of exemplified

temperature changes in the femoral artery and vein. In accordance with the principles of the system, the temperature of a limb, such as the calf muscles and lower limbs are lowered while leaving the rest of the body unaffected. In this way, the coagulation factors for blood, especially slow moving blood which is at greatest risk of clotting, will be altered sufficiently to reduce the risk of DVT forming. In the illustrated form of the example, the blood temperature of the femoral artery is cooled by the cooling device in the distal wraps (14, 16), whereas a proximal region of the limb is able to be heated via the proximal wrap 18. The cooling of the femoral artery (shown in the illustrated form as reducing from 37 degrees C to 33 degrees C) occurs from the external cooling applied from the wraps 14, 16. This external cooling also has an impact on the blood temperature of the returning femoral vein and at the extremity of the leg, the temperature in the femoral vein is 33 degrees C in the example shown. However, by virtue of the counter-current heat exchange between the artery and vein, the blood temperature in the femoral vein will be warmed (as it takes in heat from the cooling blood in the femoral artery) as it returns along the leg. In the illustrated form, this temperature may increase to 36 degrees C. The temperatures in these deep venous structures are assessed from the monitoring of the skin temperature and this information is fed back to the controller. If the returning temperature in the femoral vein remains too low, corrective action may be taken to ensure the cooling of the limb is remaining sufficiently localised (and not adversely affecting the core temperature). This may occur by reducing the rate and/or extent of cooling of the distal wraps (14, 16) or increasing the blood temperature in the femoral vein by applying heating to the surface of the patient through the proximal wrap 18.

Figs. 3 to 5 illustrate a further embodiment of a system 50 for inhibiting blood coagulation by controlled localised cooling. Unlike the system 10 of the earlier embodiment where the localised cooling was confined to a limb to reduce the likelihood of DVT, the system 50 is for cooling of blood in the brain to prevent coagulation (such as to reduce the risk of coagulation following surgery or following a thrombotic event - such as a stroke).

A primary distinguishing feature in the second embodiment over the first embodiment is the direct vascular treatment. Unlike the earlier embodiment where the cooling occurred by the cooling device being applied to the patient’s skin, the system 50 uses one or more implants (52, 54) that are located in close proximity to the vessel (in the illustrated form being the carotid artery 101). In this way the treatment (being heating, cooling or monitoring) is applied specific to the blood flow in artery.

In the embodiment in Fig.3, the implant 52 is designed to cool the blood in the carotid artery 101. In this way, blood flowing into the brain is cooled and similar to the previous embodiment, the cooling process is controlled by a controller (not shown) to reduce the blood temperature to a threshold level. To maintain the blood cooling localised, in the embodiment of Fig. 3 a heating cuff 58 is located around the patient’s neck proximally to the implant 52 to further assist in warming the blood in the jugular 102 to thereby ensure the core body temperature is not unduly affected. Again, the heating cuff is controlled from the controller in response to measured blood temperature in the jugular 102.

Fig. 4, discloses a further variation where a heating implant 54 is used in close proximity to the jugular 102 in place of the heating cuff. In this way system 50 enables both cooling and heating to be applied directly to the respective vascular structures.

Fig. 5 illustrates three versions of the cooling implant 52 that may be used in the system 50. 52A is an implant that uses a thermoelectric pad (such as a peltier cooler). 52B is an implant that incorporates fluid passages 60 to receive a cooling fluid, whereas implant 52C is in the form of a needle 62 that is arranged to pierce the artery and which includes a cooling element at its distal end 64.

Accordingly, the systems 10, 50 allow for inhibiting blood coagulation in a limb or other region of a patient by reducing the blood temperature below a level in the vascular structures and confining the cooling of the blood temperature to the vicinity of the limb or region so as not to reduce the core body temperature to a level that would negatively impact on the patient.

Variations and modifications may be made to the parts previously described without departing from the spirit or ambit of the disclosure.

In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word“comprise” or variations such as“comprises” or “comprising” is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.

Claims

1. A method of inhibiting blood coagulation in a patient comprising;

- reducing the blood temperature below a first threshold in the

vascular structures of at least a first region of the patient; and

- monitoring at least one characteristic of a second region of the patient.

2. A method according to claim 1, wherein the second region is closer to a core of the patient than the first region.

3. A method according to claim 1 or 2, further comprising increasing the blood temperature of the patient when the monitored characteristic at the second region is outside at least one parameter.

4. A method according to claim 3, wherein the step of increasing the blood temperature comprises reducing the rate and/or extent of cooling of the blood in the first region.

5. A method according to claim 3 or 4, wherein the step of increasing the blood temperature comprises applying heating to the surface of the patient.

6. A method according to claim 5, wherein the first and second regions are located on a limb of the patient and the heating is applied to a proximal region of the limb that is closer to the core of the patient than the first region.

7. A method according to any preceding claim, wherein the first region is the lower leg and the blood temperature in the femoral artery is reduced to below the first threshold.

8. A method according to any preceding claim, wherein the first threshold is established so as to reduce the propensity of the blood to coagulate.

9. A method according to any preceding claim, wherein the first threshold is at or below 36 degrees C, preferably at or below 35 degrees C.

10. A method according to any preceding claim, wherein the first threshold is at or below 34 degrees C, preferably between 31 and 34 degrees C.

11. A method according to any preceding claim when dependent on claim 7, wherein the second region is a proximal region of the leg that is closer to the core of the patient than the first region.

12. A method according to any preceding claim, wherein the monitored

characteristic is the blood temperature in the vascular structures of the second region.

13. A method according to claim 12, wherein the at least one parameter is below a second threshold temperature, the second threshold temperature being above the first threshold temperature.

14. A method according to claim 13, wherein the second threshold is at or above about 36 degrees C.

15. A method according to any one of claims 12 to 14, when dependent on claim

11, wherein the monitored characteristic is the blood temperature in the femoral vein at the proximal region of the limb.

16. A method according to any one of claims 12 to 15, wherein the monitored characteristic is established from an at least one noninvasive or minimally invasive measurement at the second region.

17. A method according to any preceding claim, wherein information indicative of the blood temperature of the vascular structures at the first and/or second region is established from at least one noninvasive or minimally invasive measurement.

18. A method according to claim 16 or 17, wherein the information indicative of the blood temperature is established from measuring the skin surface temperature and correlated using one or more characteristics of the patient.

19. A method according to claim 18, wherein the patient characteristics includes any one or more of BMI, leg diameter, body mass, ethnicity, age, sex, cardiac output, blood pressure, skin pinch thickness.

20. A method according to any one of claims 17 to 19, wherein the information indicative of the blood temperature is established from measuring blood viscosity, such as by using doppler ultrasound technique.

21. A method according to any one of claims 17 to 20, wherein the information indicative of the blood temperature is established from measuring muscle fasciculations.

22. A method according to any one of claims 17 to 21, wherein the information indicative of the blood temperature is established from using pulse oximetry to measure metabolic response.

23. A method according to any preceding claim, further comprising providing a coagulation response of the patient’s blood to alterations in blood temperature.

24. A method according to claim 23, wherein the coagulation response is

determined from a preintervention procedure.

25. A method according to claim 23 or 24, wherein the first threshold is established based on the patient’s coagulation response.

26. A method according to any preceding claim, wherein the first region is a limb and the method further comprises applying compression to the limb.

27. A method according to claim 26, wherein the compression applied is

modulated with the reducing of the blood temperature such that resultant blood temperature of the limb is maintained within a predetermined range.

28. A method according to any preceding claim, wherein the method further comprises monitoring the resistance of the first region to temperature transfer to the blood within the vascular structures.

29. A method according to any preceding claim, wherein the method further comprises collecting data of a patient response whilst the blood temperature in the vascular structures of at least the first region is reduced.

30. A method according to any preceding claim wherein the method reduces the risk of DVT in the first region.

31. A method of reducing the risk of DVT in a limb susceptible to DVT

comprising reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the limb so as to reduce the propensity of the blood in the first region of the limb to coagulate.

32. A method according to claim 31, wherein the cooling of the blood temperature is controlled to remain localised to the first region.

33. A method of inhibiting blood coagulation in a region of a patient including reducing the blood temperature below a first threshold in the vascular structures of at least a first region of the patient; and monitoring blood temperature in the region by monitoring one or more characteristics of the patient through at least one noninvasive measurement; and a processor for establishing information indicative of the blood temperature of the vascular structures of the region from the one or more characteristics.

34. A method according to claim 33, wherein the one or more characteristics comprise one or more of skin surface temperature, muscle fasciculation, metabolic response and blood viscosity.

35. A method according to any one of claims 31 to 34 and otherwise as claimed in claims 1 to 30.

36. A method according to any preceding claim, where in the blood temperature is reduced in the deep vascular structures of the first region.

37. A system for monitoring blood temperature in a region comprising one or more sensors for monitoring one or more characteristics of the patient at the surface of one or more regions on the patient; and a processor for establishing information indicative of the blood temperature of the deep vascular structures of the region from the one or more characteristics.

38. A system for inhibiting blood coagulation in a patient comprising:

- a cooling device for reducing the blood temperature in the vascular structures of at least a first region of the patient; and

- a controller for controlling the cooling device in reducing the blood temperature in the vascular structures of the first region and / or restoring of the blood temperature in the vascular structures of a second region of the patient that is closer to a core of the patient.

39. A system according to claim 38, further comprising one or more sensors for monitoring one or more characteristics of the patient; and a processor for establishing information indicative of the blood temperature of the vascular structures from the one or more characteristics.

40. A system according to claim 39, wherein the one or more characteristics

comprise one or more of skin surface temperature, muscle fasciculation, metabolic response and blood viscosity.

41. A system according to claim 38 or 40 wherein the controller is responsive to the information from the processor indicative of blood temperature.

42. A system according to any one of claims 37 to 41, further comprising a

heating device for restoring the blood temperature in the vascular structures of the patient.

43. A system according to claim 42, wherein the controller is operative to control the heating device to restore the blood temperature in the vascular structures of a second region of the patient

44. A system according to claim 43, wherein the second region is closer to a core of the patient.

45. A system according to any one of claims 38 to 44, when dependent on claim 38, wherein the cooling device is formed as part of a garment that is applied over the patient.

46. A system according to any one of claims 38 to 44, when dependent on claim 38, wherein the cooling device is an implantable device.

47. A system according to any one of claim 38 to 46, wherein the blood temperature is reduced in the deep vascular structures.

48. A system according to any one of claims 37 to 47, for use in a method according to any one of claims 1 to 36.