Bedside Point of Care Coagulation Testing for Individualized

JOURNAL OF CARDIOVASCULAR DISEASE VOL.1 NO.1 JULY 2013 IS ISSN: 2326-3121 (Print) 2326-313X (Online) http://www.researchpub.org/journal/jcvd/jcvd.html

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Abstract — A delay in surgery due to laboratory

abnormalities may increase mortality in patients with hip

fracture. In order to optimize the logistics for urgent

surgery in patients with hip fractures and anti-vitamin K

treatment, individualized doses of a Prothrombin

Concentrate were guided by a bedside whole blood

prothrombin time test.

Thirty patients with emergency hip fracture and

preoperative anti-vitamin K treatment (warfarin) due to

atrial fibrillation were studied during a 3 years period

(2010-2012). Intravenous vitamin K was recommended as

early as possible after admission at the hospital and after

diagnosis of the hip fracture by X-ray, but was not

controlled by the authors. Preoperatively the patients were

treated with repeated doses of 500 units (U) prothrombin

complex factor concentrate (PCC) if laboratory

Prothrombin Time International ratio (PT-INR) >1.5 and

orthopedic surgents urged for immediate surgery.

Simultaneosly whole blood PT-INR and activated

prothrombin partial thromboplastin time (aPTT) was

checked with a bedside point-of-care HEMOCHRON Jr

with blood from the citrated vacutainer test tubes, before

these were sent to the laboratory. Both types of PT were

checked 10 minutes after the intravenous PCC injection.

The correlation coefficient between routine citrated

plasma PT and the whole blood citrated HEMOCHRON®

PT was 0,88 (p>0,001). All patients underwent surgery

within 24 hours. No plasma was used. Vitamin K was used

in 20 of the patients and reduced the need/doses of PCC as

compared to patients with no vitamin K treatment. Five mg

of iv vitamin K was more effective than 2 mg iv in reducing

the need for PCC.

Cite this article as: Thomas A, Schött U. JCvD 2013;1(1):8-12

Keywords — Point of Care, whole blood PT, prothrombine

complex concentrate, warfarin reversal, hip surgery.

This work was supported by ISEX-ALF, Lund University. Received on 05 May 2013. From the Department of Anesthesiology and

Intensive Care, Skane University Hospital and Lund University, Lund, (OT,

SU). *Correspondence to Prof. U. Schött (e-mail: [email protected]).

I. INTRODUCTION

ip fracture is a common clinical problem that leads to

considerable mortality and disability. Comorbidity is more

important for mortality in the elder patients undergoing surgery

than age itself.1-3

Whether reducing time-to-surgery for elderly

patients suffering from hip fracture results in better outcomes

remains subject to controversial debates. Many case series

support early surgical repair, although patients who would

benefit from delay and further medical work-up have not been

well identified.3, 4-7

. Shorter time-to-surgery may be associated

with somewhat lower rates of post-operative complications

such as decubitus ulcers, urinary tract infections, thrombosis,

pneumonia and cardiovascular events, and with somewhat

higher rates of others such as post-operative bleeding or

implant complications.8 It also shortens the hospital stay.

9

In the study by Kirsch et al10

geriatric patients on warfarin

before sustaining orthopedic injuries were compared with

matched control patients not on warfarin. In comparison with

the control group, significant differences were found in time

delay from admission to surgery, hospital length of stay, total

units of blood transfused, and discharge disposition. No

difference was found in number of intensive care unit days,

complications or mortality.

Clinicians are frequently called on to correct this coagulopathy

in patients receiving oral anticoagulation therapy. Before

elective surgery, anticoagulation reversal may be undertaken

over several days by discontinuing warfarin or vitamin K

treatment, but rapid correction is required in emergency.

Compared with human fresh frozen plasma (FFP), prothrombin

complex factor concentrate (PCC) provides quicker correction

of the international normalized ratio (INR) and improved

bleeding control. Although many patients who require rapid

reversal of warfarin are currently treated with FFP, PCC should

be considered as the proper therapy.11

The standardized test used for evaluating the effect of warfarin

is the prothrombin time (PT), which is measured and expressed

by INR. Delay in collecting coagulation test results from a

central laboratory is one of the critical issues to efficiently

control haemostasis during surgery. Portable point-of-care

Bedside Point of Care Coagulation Testing for

Individualized Antivitamin K Reversal:

A Prospective Study

Owain Thomas, Ulf Schött*

H

mailto:[email protected]


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(POC) analytical instruments for measurement of capillary

whole blood PT have been available for the last decades. In a

study by Toulon et al12

a POC-based PT was in good agreement

with central laboratory test result. On-site PT monitoring did

not significantly change FFP transfusion in patients when

compared to use of central laboratory monitoring. Test results

were obtained in less than 5 minutes when performed using the

POC device versus a median turnaround time of 88 minutes

when blood collection tubes were sent to the central

laboratory.12

In the present study, we studied warfarin reversal with bedside

individualized titration of the PCC dose being guided by a

POC-PT test. This was performed in the operation ward

immediately before surgery.

II. METHODS

Thirty hip fracture patients on anti-vitamin K treatment

(warfarin) were studied. Approval was obtained from the

Regional Ethical Review Board (Lund, Protocol DNR

2010/482) and informed consent was taken from all the patients.

The project was graded as a valuable clinical project, but not a

research project per se by the Regional Ethical Review Board.

During the project period 2010-12 a logistic scheme was

introduced at the Lund University Hospital to enable surgery

within 24 hours after admission.

Vitamin K was recommended as early as possible after

admission at the hospital and after diagnosis of the hip fracture

by X-ray, but was not controlled by the authors. All hip

fractures underwent surgery within 24 h after admission.

Blood was sampled from large gore indwelling venous

catheters; first blood was discarded. Blood samples were

collected into citrated plastic vacuum tubes (BD Vacutainer®

Coagulation Tube, 2.7 ml, (3.2% citrate, BD Vacutainer

systems, Plymouth, UK). Fifteen microliters of the 2.7 ml

citrate blood sample were used to analyze POC-PT, followed

by another 15 microliters for POC-activated partial

thromboplastin time (aPTT) with a bedside POC blood test

device, HEMOCHRON Jr (ITC, USA). Then, the blood tube

was sent to laboratory for centrifugation and the citrated plasma

used for standard laboratory PT.

Laboratory PT-INR was performed using a combined

thromboplastin reagent (Stago prothrombin complex assay,

SPA+, Stago). The Owren PT assay was calibrated using INR

calibrators certified by the Swedish external quality assessment

organization (Equalis, Uppsala, Sweden). The reference range

for PT (INR) is 0.9–1.2.

The HEMOCHRON Jr. microcoagulation system relies on a

mechanical endpoint clotting mechanism in which testing

occurs within disposable PT/aPTT cuvettes.

The instrument precisely measures 15 microliters of blood and

automatically moves it into the test channel of the PT cuvette.

Sample/reagent mixing and test initiation are performed

automatically, eliminating the need for operator interaction.

After mixing with the reagent, the sample is then moved back

and forth within the test channel and monitored by the analyzer

for clot formation. Electronic optical detection of a fibrin clot in

the blood sample automatically terminates the test. The

instrument reports the whole blood number mathematically

converted INR and plasma equivalent value in seconds in order

to provide a familiar clinical format and thus facilitating

accurate clinical test result interpretation. Daily quality controls

were performed on the instruments with Electronic System

Verification Cartridges.

Immediately pre-operatively the patients were first treated with

500 units (U) of a PCC (Confidex, CSL Behring) if laboratory

and HEMOCHRON Jr PT-INR were >1.5. POC-PT and

laboratory PT were checked 10 minutes after the intravenous

PCC injection (injection rate 250 U/minute). Supplementary

doses of PCC (500 U at a time) were given if the initial PCC

dose failed to reduce HEMOCHRON Jr-INR <1.5. Laboratory

PTs were analyzed with a 30 minutes delay and were only used

as a control during this titration procedure. Postoperatively

laboratory PT-INR was controlled in the ward as well as

development of wound oozing/haematoma and need for more

AVK reversal with additional doses of vitamin K or further

doses of PCC.

III. RESULTS

All patients underwent surgery within 24 hours. No bleeding

complications were seen. No plasma was used. Intravenous K

vitamin was used preoperatively in 20 of the patients. K vitamin

injection reduced the need for PCC as seen in Table 1. Table 1

identifies actual doses of PCC to normalize PT-INR <1,5. Five

mg of iv vitamin K was more effective than 2 mg iv in reducing

the need for PCC.

Fig. 1. Correlation between citrated preoperative whole blood POC-PT and citrated laboratory PT.

In the 10 patients not receiving preoperative vitamin K,

additional doses of 2 mg vitamin K were administrated up to 8

hours postoperatively in 6 patients with laboratory

PT-INR >1.5, and 3 of those patients received additional PCC


10

(500 U) to counteract active oozing from wound (no drainages).

No wound haematomas or reoperations were needed. Warfarin

was reinstalled on day 2 after surgery and PT-INR became

therapeutical (>2.0) on day 6 in all patients. No trend in delay to

achieve PT-INR >2.0 was noted in patients that had received

the higher dose of vitamin K (5mg) as compared to the lower

dose (2mg).

Figure 1 shows the correlations between routine laboratory

PT-INR and POC-PT from 30 venous citrated samples

analysed preoperatively. The correlation coefficient between

routine citrated plasma PT and the whole blood citrated

HEMOCHRON® PT was 0,88 (p>0,001). Correlation was

lower between POC-PT and POC-aPTT. In some of the patients

with PT-INR<1.5; POC-aPTT was higher than our laborartory

plasma aPTT reference level (>37s). POC-PT-INRs were all

ready after 5 minutes from sampling as compared to the 30

minutes for laboratory PT-INR.

IV. DISCUSSION

The bedside titration of PCC reduced time to surgery and

enabled surgery according to logistics within 24 hours of

admission. K vitamin injection reduced the need for PCC. No

bleeding complications were seen. There was a significant

correlation between routine citrated plasma PT and the whole

blood citrated HEMOCHRON®-PT. POC-aPTT seemed to be

prolonged as compared to POC-PT, but the ITC website defines

whole blood normal range to 62.8-88 s as compared to plasma

normal range of 23.2-38.7. There are no published studies on

effects of warfarin reversal with PCC/vitamin K on whole

blood aPTT nor correlating it to laboratory aPTT methods. Also

the aPTT reagent use in the HEMOCHRON®

-aPTT is not

disclosed. There are more than 8 aPTT reagents on the market

with different reference values and dose responses to

anticoagulants. Therefore it is important to address this issue.

Bleeding complications with anticoagulant drugs appear to

occur more frequently in older patients than in younger

individuals.13

Advanced age (>75 years), intensity of

anticoagulation (INR>4.0), history of cerebral vascular disease

(recent or remote), and concomitant use of drugs that interfere

with haemostasis [aspirin (acetylsalicylic acid) or nonsteroidal

anti-inflammatory drugs] are among the most important

variables in determining an individual's risk for major bleeding

with anticoagulants. Older patients often display increased

sensitivity to the effects of warfarin, both in the early induction

phase and during the long-term maintenance phase of therapy.

Conditions such as congestive heart failure, malignancy,

malnutrition, diarrhoea and unsuspected vitamin K deficiency,

enhance the PT response. The decision to interrupt

anticoagulant therapy before elective surgery in elderly patients

should evaluate the thrombotic risk of such a manoeuvre versus

the risk of bleeding if anticoagulants are continued.

Fig. 2. Correlation between preoperative citrated whole blood POC-aPTT and POC-PT-INR

There is little consensus on the optimal perioperative

management for most patients on oral anticoagulation with

vitamin K antagonists.14

Bridging therapy is not recommended

for the majority of patients on oral anticoagulation as most are

at low risk for perioperative stroke. Though most clinicians

choose an aggressive perioperative strategy for patients with

high thromboembolic risk (e.g., mechanical mitral valve

replacement) by withholding warfarin perioperatively and

using full-dose heparin, prophylactic dose heparin is given for

lower risk categories (e.g., bi-leaflet aortic valve replacement

and atrial fibrillation). The amount of increase in postoperative

major bleeding when full-dose anticoagulation is administered

soon after surgery is the main factor in the decision with the

least available data. The optimal method for returning the

PT-INR to the desired range preoperatively depends upon its

degree of initial elevation and whether or not clinically

significant bleeding is present.

Baseline PT-INR, but not the size of the maintenance dose, is

associated with the rate of normalization of PT after stopping

warfarin, but it has limited utility as predictor in clinical

practice. Whenever normal haemostasis is considered crucial

for the safety, the INR should be checked again before the

invasive procedure.15

Rapid reversal of excessive anticoagulation should be

undertaken in patients with serious bleeding at any degree of

anticoagulation.. Since the effect on the PT-INR becomes

visible only after 1-3 hours (after intravenous injection, longer

duration after oral administration), vitamin K is often

overlooked in the acute situation. Early conversant vitamin K

treatment, preferably intravenously in severe, life-threatening

bleeding, reduces the need for further correction needs to factor

concentrates and plasma.


11

The literature suggests that unresponsiveness to warfarin can

continue for 1 week or longer after administration of high-dose

(10 mg or greater) vitamin K1. However, there is a lack of

supporting data to define the duration and clinical

consequences of impaired warfarin response with high doses of

vitamin K1 in this setting.

In a case series,16

four patients receiving indefinite warfarin

therapy had received high and, in most cases, repeated doses of

vitamin K1 for urgent reversal of therapeutic anticoagulation

for an invasive procedure or surgery. The patients displayed

impaired warfarin response for 11 days-3.5 weeks after

administration of vitamin K1 (10-40 mg). The associated

financial burden for the patients was substantial.

Warfarin reversal with vitamin K was successful and facilitated

earlier surgery in a study by Tharmarajah et al.17

The first dose

was effective in approximately three quarters of patients. The

mean time to surgery in warfarin treated patients not given

vitamin K was 111.9 hours; in the intervention group, it was

67.4 hours, giving a mean difference of 44.5 hours (P = 0.01).

Vitamin K reduced the PT-INR to less than 2.0 in 74% of

patients within 24 hours. There were no complications of

vitamin K administration. A dose of vitamin K costs

approximately 1/1000 of a hospital bed day cost. A loading

dose of warfarin on the second postoperative day took

approximately 1 day longer to reach an INR of greater than 2.0

in the intervention patients than in those who had not been

given vitamin K.

The advantage in serious bleeding is that the PCC can be

administered rapidly (10-15 minutes); for FFP 1-2 hours are

needed for blood sampling, blood typing / base test and thawing

of FFP.11-12

A more complete reversal of their anticoagulation is

also seen as compared with FFP. Sometimes the recommended

plasma dose of 10-15 ml/kg bodyweight is insufficent and

doses up to 30 ml/kg bodyweight have been reported.18-20

Although there are historic concerns regarding potential

infectious and thrombotic risks with PCCs, current PCC

formulations are much improved. Recombinant activated factor

VII is a potential alternative to PCCs, but PCCs are more

cost-effective in correcting warfarin-induced coagulopathies.

Empiric treatment with PCC doses according to logarithms

adapted to differently prolonged PT-values has been

suggested.15

To compare the efficacy of a "standard" dosage of

20 ml PCC equivalent to about 500 IU factor IX (group A), and

an "individualized" dosage based on a target-INR of 2.1 or 1.5,

the initial-INR and the patient's body weight (group B) were

studied by Schulman.13

PCC and Vitamin K (10 mg) were

administered intravenously. The number of patients reaching

the target-INR 15 min after the dosage of PCC was

significantly higher in the group treated with an

"individualized" dosage, compared to the group treated with a

standard dose (89% versus 43%).

A surgical procedure should probably not be performed on

patients with a PT-INR level above 1.5.19

This probably

depends on the type of surgery and if regional anaesthesia like

spinal or epidural anaesthesia is considered.20

There are few

publications on the optimal PT/aPTT when spinal anaesthesia

is safe and national guidelines may differ. Furthermore, there is

insufficient evidence available from trials comparing regional

versus general anaesthesia to rule out clinically important

differences. Regional anaesthesia may reduce acute

postoperative confusion but no conclusions can be drawn

concerning mortality or other outcomes.21

A lot of plasma is

used to correct high PT-INRs preoperatively to favour spinal

anaesthesia – this needs to be further studied.

More patients do get hip protheses initially – half or whole

prostheses, and this type of surgery bleed more than nailing,

plates or compressive screws.22,23

With the simpler procedures

higher PT-values have been suggested, but are not well studied.

Cementing prostheses in place seems to reduce pain

post-operatively and results in better mobility, but because of

the under-reporting of outcomes and the small number of

patients involved, no definite conclusions can be made.24

It is

also notable that of all patients with a postoperative hemoglobin

level less than 100 g/L, a majority had the most complicated

types of fractures and were operated on with a screw and plate

fixation, yet only 65% of the patients had blood transfusions.25

The role of bipolar prostheses and total hip replacement is

uncertain. Further well-conducted randomized trials are

required.

The use of POC testing in critical care patient units has

continued to increase since the 1980s. This increase is due to

the need for prompt therapeutic interventions that may impact

mortality and morbidity, and reduce the overall cost of

healthcare for critically ill patients.26

Many primary care

laboratories use POC instruments to monitor patients on

anticoagulant treatment. In one study,27

empirical data from 18

primary care laboratories used the POC instruments

Thrombotrack, Coagu-Chek S, or Hemochron Jr. Signature.

The total within-lab coefficient of variation was 3.8% and 6.9%

for Thrombotrack, 8.9% and 10.5% for CoaguChek S, and

9.4% and 14.8% for Hemochron Jr. Signature for the control

sample measurements and the split sample measurements,

respectively.

In a study by Toulon et al12

POC-based PT was in good

agreement with central laboratory test result with coefficient of

correlation in the range from 0.711 to 0.960. Comparison was

less conclusive when PT was expressed in seconds and for

aPTT, with significantly shorter clotting times and lower ratios

obtained on the POC device. On-site PT (in activity percentage)

monitoring would have induced no significant change in FFP

transfusion in patients when compared to central laboratory

monitoring. Test results were obtained in less than 5 minutes

when performed using the POC device versus a median

turnaround time of 88 minutes (range: 29-235 minutes) when

blood collection tubes were sent to the central laboratory. These

results suggest that, in providing a rapid answer, POC-based


12

monitoring of PT (in percentage) using the CoaguChek device

could be validly used in patients undergoing haemorrhagic

surgical procedures.

Wieloch et al28

studied PT-INR values obtained by a new

point-of-care device CoaguChek XS, to Owren PT in a hospital

setting. The mean PT-INR difference (S.D) was 0.02 (0.22).

The CoaguChek XS presents reproducible, highly comparable

results with Owren PT at therapeutic levels of PT-INR with a

correlation factor r=0.94; p<0.001. The CoaguChek XS seems

to produce better results than the earlier CoaguChek S,

probably due to a new method of PT measurement where levels

of fibrinogen and haematocrit do not affect the outcome.

V. CONCLUSIONS

The bedside titration of PCC will probably increase the cost

benefit of PCC treatment instead of giving a standard dose of

PCC.29

Further studies should focus on, whether a PT-INR goal

in hip fracture of >1.8-2 is safe for the surgical procedure (not

spinal anesthesia). Also the time necessary to maintain a

decreased PT-INR around surgery needs to be studied. Use of

POC-PT in the emergency ward and repetitive use in the ward

prior to surgery could favor titration of vitamin K doses, also

repeated doses. This also holds for optimal PT-control in the

immediate postoperative period and in the later warfarin

reinstitution phase.

REFERENCES

[1] Hannan EL, Magaziner J, Wang JJ, Eastwood EA, Silberzweig SB,

Gilbert M, Morrison RS, McLaughlin MA, Orosz GM, Siu AL. Mortality

and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes. JAMA. 2001;285:2736-42.

[2] McLaughlin MA, Orosz GM, Magaziner J, Hannan EL, McGinn T,

Morrison RS, Hochman T, Koval K, Gilbert M, Siu AL. Preoperative status and risk of complications in patients with hip fracture. J Gen Intern

Med. 2006;21:219-25.

[3] Morrison RS, Chassin MR, Siu AL. The medical consultant's role in caring for patients with hip fracture. Ann Intern Med. 1998;128:1010-20.

[4] Rogers FB, Shackford SR, Keller MS. Early fixation reduces morbidity

and mortality in elderly patients with hip fractures from low-impact falls. J Trauma 1995;39:261–5.

[5] Orosz GM, Magaziner J, Hannan EL, Morrison RS, Koval K, Gilbert M,

McLaughlin M, Halm EA, Wang JJ, Litke A, Silberzweig SB, Siu AL. Association of timing of surgery for hip fracture and patient outcomes. J

Am Med Assoc 2004;291:1738–43.

[6] Julebø V, Bjøro K, Krogseth M, Skovlund E, Ranhoff AH, Bruun TB. Risk factors for preoperative and postoperative delirium in elderly

patients with hip fracture. J Am Geriatr Soc 2009;57:1354–61.

[7] Bottle A, Aylin P. Mortality associated with delay in operation after hip fracture: observational study. Br Med J 2006;332:947–51.

[8] Smektala R, Endres HG, Dasch B, Maier C, Trampisch HJ, Bonnaire F,

Pientka L. The effect of time-to-surgery on outcome in elderly patients with proximal femoral fractures. BMC Musculoskelet Disord.

2008;9:171.

[9] Siegmeth AW, Gurusamy K, Parker MJ. Delay to surgery prolongs hospital stay in patients with fracture of the proximal femur. J Bone Joint

Surg 2005;87:1123-6.

[10] Kirsch MJ, Vrabec GA, Marley RA, Salvator AE, Muakkassa FF.

Preinjury warfarin and geriatric orthopedic trauma patients: a

case-matched study. J Trauma. 2004;57:1230-3.

[11] Levy JH, Tanaka KA, Dietrich W. Perioperative hemostatic management

of patients treated with vitamin K antagonists. Anesthesiology. 2008;109:918-26.

[12] Toulon P, Ozier Y, Ankri A, Fléron MH, Leroux G, Samama CM.

Point-of-care versus central laboratory coagulation testing during haemorrhagic surgery. A multicenter study. Thromb Haemost.

2009;10:394-401.

[13] Sebastian JL, Tresch DD. Use of oral anticoagulants in older patients. Drugs Aging. 2000;16:409-35.

[14] Angelo M, Stockner I, Wiedermann CJ. [Bleeding risk and perioperative

management of patients anticoagulated with vitamin K antagnosists]. Wien Med Wochenschr. 2008;158:615-20.

[15] Schulman S, Elbazi R, Zondag M, O'Donnell M. Clinical factors

influencing normalization of prothrombin time after stopping warfarin: a retrospective cohort study. Thromb J. 2008;16:6-15.

[16] Fugate SE, Nichols CM, Cudd LA. Impaired warfarin response secondary

to high-dose vitamin K1 for rapid anticoagulation reversal: case series and literature review. Pharmacotherapy. 2004;24:1213-20.

[17] Tharmarajah P, Pusey J, Keeling D, Willett K. Efficacy of warfarin

reversal in orthopedic trauma surgery patients. J Orthop Trauma. 2007;21:26-30.

[18] Chowdhury , Saayman AG, Paulus U, Findlay GP, Collins PW. Efficacy

of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J

Haematol 2004;125:69-73.

[19] Williams TM, Sadjadi J, Harken AH, Victorino GP. The necessity to assess anticoagulation status in elderly injured patients. J Trauma.

2008;65:772-6.

[20] Hantler C, Despotis GJ, Sinha R, Chelly JE. Guidelines and alternatives for neuraxial anesthesia and venous thromboembolism prophylaxis in

major orthopedic surgery. J Arthroplasty. 2004;19:1004-16.

[21] Parker MJ, Handoll HH, Griffiths R. Anaesthesia for hip fracture surgery in adults. Cochrane Database Syst Rev. 2004;18:CD000521.

[22] Foulongne E, Gilleron M, Roussignol X, Lenoble E, Dujardin F.

Mini-invasive nail versus DHS to fix pertrochanteric fractures: a case-control study. Rev

Chir Orthop Traumatol. 2009;95:592-8.

[23] Parker MJ, Gurusamy K. Arthroplasties (with and without bone cement) for proximal femoral fractures in adults. Cochrane Database Syst Rev.

2004;2:CD001706.

[24] Yamada T, Momwaki K, Shmroyama K, Ohtani T, Sakai A, Miki T, Kobayashi M. High incidence of cardiorespiratory deterioration in

patients receiving cemented hip hemiarthroplasty for femoral neck

fracture. Masui. 2007;56:810-6. [25] Björkelund KB, Hommel A, Thorngren KG, Lundberg D, Larsson S. The

influence of perioperative care and treatment on the 4-month outcome in

elderly patients with hip fracture. AANA J. 2011;79:51-61.

[26] Yuoh C, Tarek Elghetany M, Petersen JR, Mohammad A, Okorodudu AO. Accuracy and precision of point-of-care testing for glucose and

prothrombin time at the critical care units. Clin Chim Acta.

2001;307:119-23. [27] Stavelin A, Petersen PH, Sølvik U, Sandberg S. Internal quality control of

prothrombin time in primary care: comparing the use of patient split

samples with lyophilised control materials. Thromb Haemost. 2009;102:593-600.

[28] Wieloch M, Hillarp A, Strandberg K, Nilsson C, Svensson

PJ.Comparison and evaluation of a Point-of-care device (CoaguChek XS) to Owren-type prothrombin time assay for monitoring of oral

anticoagulant therapy with warfarin. Thromb Res. 2009;124:344-8.

[29] van Aart L, Eijkhout HW, Kamphuis JS, Dam M, Schattenkerk ME, Schouten TJ, Ploeger B, Strengers PF. Individualized dosing regimen for

prothrombin complex concentrate more effective than standard treatment

in the reversal of oral anticoagulant therapy: an open, prospective randomized controlled trial. Thromb Res. 2006;118:313-20.

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Bedside Point of Care Coagulation Testing for Individualized