Summary of MedSun Reports Describing Adverse Events With Coagulation Monitoring Devices
MedSun: Newsletter #40, September 2009

By Ahmed Haque, Patient Safety Staff, 2009

Coagulation monitoring devices offer a way to monitor the tendency and rate of an individual’s formation of blood clots. For millions of patients at risk of thrombosis or embolism, the information provided by these devices is critical in regulating the levels of anticoagulants physicians must administer. Imprecise figures or estimates can lead to dangerous results on both the high and low side of the dosing spectrum. Too much anticoagulation can lead to serious hemorrhaging and bleeding, while too little anticoagulation can lead to equally serious blood clots. Most coagulation monitors function by mixing small samples of blood via capillary or venipuncture with a set of “activating” reagents. These reagents initiate the “clotting cascade” of the blood sample. Based on how quickly the resulting blood mixture clots, the device will output a reading to be interpreted by a physician. Due to varieties in reagents and technologies used by the devices, differences in value can sometimes occur between devices. (1,2,3)

Over the past 5 years, MedSun has received 10 adverse event reports associated with coagulation monitoring devices. The reports represent the products of 5 manufacturers: International Technidyne Corporation (3), HemoSense Inc. (2), Diagnostica Stago Inc. (2), Beckman Coulter Inc. (2), and Dade Behring Inc.(1). They were submitted by 8 hospitals between September, 2004 and March, 2009.

The reported device problems include:
• Unrealistic Results / Discrepant Results (between devices): 6
• Inconsistent Results (within device): 2
• Defective Component: 1
• Monitor Blanks: 1

Of note, one report noted that the ISI value used to calculate INR results was being scanned from the bar code improperly, yielding incorrect results.

During this time period there were no reported deaths associated with these devices. Two reports indicated that treatment adjustments were based on false readings. In both reports, serious injuries resulted from the change in treatment.

The reported patient injuries include:
• Acute hemorrhaging due to high coumadin
• Syncope requiring hospitalization due to high coumadin

Of the reports that listed patient age, two had a patient age listed as less than 21 years and five had a patient age listed as greater than 21 years. Of the reports that listed patient gender, one report involved a female patient and a total of five reports involved male patients.

These MedSun reports contributed to FDA awareness of the device problems. FDA follow-up with the manufacturers may relate to the following recalls.



Recalls
Recall NumberTrade Name/Product Recall Class Date Intiated Date Posted Recalling Manufacturer Reason For Recall
Z-1127-2007 Instrumentation Laboratory 2 6/19/2007 8/7/2007 Instrumentation Laboratory Co. ACL TOP unit when in emergency stop may release liquid during recovery sequence and contaminate sample tube.
Z-1422-05 STA-R blood coagulation analyzer. Catalog Number 57160. 2 6/20/2005 8/30/2005 Diagnostica Stago Inc. Concerning the STA-R blood coagulation analyzer there is a possible failure mode associated with patient samples receiving prolonged exposure time to reagents during the cuvette roll change process.
Z-0915-05 Instrumentation Laboratory 2 5/19/2005 6/21/2005 Instrumentation Laboratory Co. Patient prothrombin time (PT) may report low for individuals on anticoagulant therapy




The following table lists the MedSun reports that are described in the device problem summary above.

[Note: The reports have been edited for clarity]

Adverse Events
DeviceDevice Identifiers Event Description
International Technidyne Corporation: Hemochron Jr. Signature + None provided Cath Lab manager reports concerns with either Hemochron Jr./Signature + machines or possibly the Cuvettes which were being utilized. At time in question, Cuvette ACT+ were being used. We are now using ACT-LR. Below is a summary of what happened, but we cannot definitively say there was a "malfunction". It was reported that while using the Cuvette ACT+, the times were lower with the amount of heparin given in some procedures. Our cath lab compared results using one blood sample between two Hemachron machines and a different mfr's machine. In one particular instance, the sample results were: The different mfr's machine read 219, Hemochron (both machines) read 171. These results were run simultaneously, side by side. The request had come from the physician when results from the same three machines, 50 minutes earlier showed the result from the different mfr's machine as 409. One of the Hemochron machines showed a result as 171 and the other Hemochron machine was not recorded. To summarize, when the cath lab used the ACT+ the times seemed to be low. We did not change our QA process and the numbers showed we were within ranges for the tests. We have since gone back to the ACT-LR and our physicians now have the confidence to believe the results.
HemoSense, Inc: INRatio PT Monitoring System None provided Patient with history of DVT x2, hypercoagulable state, and chronic treatment with Coumadin. Patient was seen in Coumadin clinic where patient was tested three times. First time the machine read "error". Test was repeated two more times with result of INR 2.2 and 2.3. Patient went to a second facility for a CT scan for an unrelated issue. CT results demonstrated acute hemorrhage with the right intrarenal collecting system. Patient went to Emergency Department with complaint, and INR result via venous draw was 10.8. Patient was treated with vitamin K and fresh frozen plasma. Patient was discharged with an INR of 2, and on Coumadin 5 mg. Patient's prior Coumadin dose was 40 mg and had been increased to 90 mg based on results obtained from HemoSense monitor.
HemoSense, Inc: INRatio PT Monitoring System None provided The patient has a history of post-op DVT and pulmonary emboli diagnosed five weeks ago after ventral hernia repair. They were treated with IV unfractionated Heparin and Coumadin at that time. He was eventually stabilized on oral Coumadin and was discharged home with instructions to continue with Coumadin 5mg po every night, and to have daily PT/INR levels called to the physician. A day prior to the event, the PT/INR level was obtained per fingerstick and the level was 1.6. The physician was contacted and he increased the Coumadin dosage to 15mg. The patient had been participating in physical therapy at home. The next day, the patient was noted to have left back pain, and shoulder discomfort along with generalized weakness. He suffered a syncopal episode and was transported to the hospital. His lab results included an hemoglobin (9.1) and hematocrit (27.1). The platelets were 199,000 and the INR was 10.5. The patient was admitted to the ICU and given Vitamin K. There were two separate HemoSense machines that could have been used and both are sequestered and will be analyzed.
Diagnostica Stago, Inc: STA Compact None provided INR results for eight days were reported out incorrectly. The ISI (International Sensitvity Index) value, which is uploaded by bar code into STA Compact was read incorrectly by the instrument. The INR (International Normalized Ratio) result is a calculated result which was reported incorrectly.
Dade Behring, Inc: CA-1500 CP Model: CA-1500 / Lot: Batch A4794 Patient samples were not reproducing or were causing errors on the instrument. Bubbles were noticed on the sample plate affecting the volume of patient specimen being tested. Multiple manufacturer service representative visits have still not solved the problem. Dade Behring's advice was to run the specimen in duplicate, which is not required per the operator's manual. The instrument used previously did not require duplicate testing. Humidity levels and specimen collection tubes have also been mentioned as possible causes for the erroneous results. Humidity levels in the lab have been increased as high as possible with no changes.
International Technidyne Corporation: Hemochron Jr. Signature None provided The hospital ran out of low range cuvettes for the device on 5/2005 when 2 patients were being tested at the same time. The manufacturer placed our order on back-order and instructed the staff to use the high range cuvettes, and reprogram the device to the high range control. They instructed staff that the results would be 20 - 25% lower using the high range cuvettes since the range is broader and this was to be taken into consideration. The patient was receiving blood products during this time as well as in response to their diagnosis. By the following week the manufacturer had located the low range cuvettes and they were shipped to our hospital. Follow up reveals that the device was reprogrammed for the low range cuvettes. Now that the low range cuvettes are being used the results are not consistent when compared to results from the central lab.
International Technidyne Corp: Hemochron Jr., Signature None provided The quality controls required before use of the Hemochron Jr. and the numbers obtained were appropriate. Subsequently, the Hemochron Jr was used to obtain an Activated Clotting Time, ACT, on a patient undergoing an angioplasty. Patient was given 2000 Units of heparin and device displayed an ACT = 152. Twenty-five minutes later, the patient was given another 1000 Units of heparin and device displayed ACT = 152. After 20 minutes, another 1000 Units of heparin were given to the patient and the ACT obtained was 169. The anesthesiologist who was monitoring the patient reports that after 4000 Units of heparin, the patient's ACT should have been approximately 200. A PTT, prothrombin time, requested from lab at the same time was greater than 106 seconds.
Beckman Coulter, Inc: MLA 1400 C Model: E1400C This event involved the heat exchanger and tubing for MLA 1400C coagulation instrument. After a long period of problems with quality control and checking everything the problem was finally narrowed down to the heat exchanger and tubing. The company acknowledged that they had changed manufacturers.
Beckman Coulter, Inc: Electra 1400C coagulation analyzer Model: E1400 C Screen monitor went blank. Beckman Coulter service person replaced monitor. Machine down 24 hours.
Diagnostica Stago, Inc: Compact None provided Sample was put on coagulation instrument to test a PTT, partial thromboplastin time. First result was greater than 300 seconds. Instrument automatically repeated the test and resulted as greater than 300 seconds for the second time. Sample was checked for clot and result turned out. No clot was found. Sample was centrifuged and repeated. Again, first result was greater than 300 then instrument auto-repeated with a result of 79.8 seconds.

Additional Information:

1. Lab Tests Online
http://www.labtestsonline.org/understanding/analytes/pt/test.html

2. Hirsh, J. & Fuster, V. Guide to anticoagulant therapy. Part 2: Oral anticoagulants. American Heart Association [published erratum appears in Circulation 1995 Jan 15; 91 (2): A55-A56]. Circulation 89, 1469–1480 (1994).

3. Yang, D.T., Robetorye, R.S. & Rodgers, G.M. Home prothrombin time monitoring: a literature analysis. Am. J. Hematol 77, 177-186 (2004).


MedSun Newsletters are available at www.fda.gov/cdrh/medsun