Coagulation Case Studies

Case Study

2009-06-04T11:46:00.002-04:00

A 42 year old female presents with symptoms of a DVT, this is her second episode.
Currently she is on oral contraception. Family history includes maternal grandmother died from a stroke at the age of 50, and mother presented with a DVT at the age of 55 after being placed on hormones for menopause.
Patient test results as follows:
PT = 10.1 (10-12 sec)
APTT = 26.1(26-36 sec)

What tests should be ordered?

Should Genetic testing be done?

Should this patient be removed from OC?

What would you do??

APRIL CASE STUDY

2009-04-05T14:27:00.002-04:00

A 68 year old women has hematuria. A PT and APTT are performed results are as follows:
PT= 34.7
APTT =88.5
1:1 mix PT = 32.2
APTT= 89.0
Thrombin Time = 12.1 (11.5-19.0)
What would be the next line of testing, possible diagnosis and treatment?

MARCH CASE STUDY

2009-03-02T22:35:00.003-05:00

Little girl with multiple problems, has a PT and APTT performed-
PT= 32 seconds
APTT =76 seconds
1:1 mix= PT= 12.1
APTT = 32.1 seconds correct into normal range
Factor deficiency?
Common pathway: II, V, and X all normal
VIII, IX, XI and XII all normal

What do these results mean?

ANSWERS TO CASE STUDIES:

We know the disorder is in the common pathway-
and that it is a factor deficiency. Both the PT and APTT correct into the normal range-
large correction- this little girl has a fibrinogen deficiency.
A thrombin time should also be performed should be prolonged-
A reptilase time will be prolonged, this will confirm no heparin on board and truly a fibrinogen deficiency.
Also, if there was heparin on board the mixing study would not correct (remember heparin is an inhibitor)
The next step is to see if this is due to a quantitative or qualitative defect of fibrinogen. If antigen testing is normal and activity is abnormal this is a dsyfunctional molecule or a qualitative defect. If both are decreased there would be a quantitative defect.
The FDA just approved treatment with fibrinogen concentrates, prior to that the treatment was cryoprecipitate.

FEBRUARY CASE STUDY

2009-02-08T14:27:00.003-05:00

A in-patient has a prolonged APTT - that is all that you know-
How do you cost effectively work up this patient- so as to maximize the information you give to the clinician and minimze the costs to the laboratory?

Your first line of testing on an inpatient is to make sure the sample is not contaminated with heparin. The best test for residual heparin is a thrombin time. If this is normal, you can proceed with your next line of testing- which would be to look for an inhibitor or a factor deficiency. If the test is prolonged, and the fibrinogen is normal, you most likely have heparin in the sample. You can request another sample, or you can treat the plasma with Hepzyme (SIEMENS) which will neutralize the heparin and you can now test the sample.
You can then go on to do your mixing study, and based on that result work up either an inhibitor or a factor deficiency.

Testing in this manner is the most cost effective way to approach this prolonged APTT.

Answers to Case Studies

2009-02-08T13:35:00.003-05:00

SEPTEMBER CASE STUDY:
Known 3 yr old hemophiliac with an APTT >100 seconds, should he get product?

When the factor VIII level was checked on this patient- the factors demonstrated an inhibitor effect- at a 1:10 dilution the APTT was 54% increasing to a level of 98% at a 1:40- why did this happen?

Based on the prolonged APTT the patient would have probably recieved product, but the inhibitor effect of the factor assays, is most likely due to heparin- and drawing the patient from a line- this is why it is important to screen inpatients and pediatric patients with a thrombin time. This test in the most sensitive test to detect heparin. The patient had already gotten product prior to being transfered to this hospital- a small detail that was not communicated.

DIAGNOSIS: SAMPLE DRAWN THROUGH A LINE, CONTAMINATED WITH HEPARIN

OCTOBER CASE STUDY
Giving a 2 year old excess coumadin is a very risky venture. You have a very high risk of the patient bleeding, not only by virtue of the excess medication, but because the child is very active and may fall. There is also the issue of non-compliance, giving a child an oral medication can be difficult- they may spit it out, or not take it, however the mother insisted that the child did take the medication. The INR did not come into range of 2.1 until the dose of coumadin was ten times what would normally be given. It decided to test the child for coumadin resistance- the child had a polymorphism that made him resistant to a normal dose, the dose that he was receiving was normal for him.

DIAGNOSIS: POLYMORPHISM- PATIENT RESISTANT TO COUMADIN

DECEMBER CASE STUDY:
Obese and sedentary cousin has pain in the leg, after a large Christmas dinner. Based on symptoms, the ER gives him a dose of heparin as a precautionary measure to prevent a possible DVT and the progression to a PE. Since imaging is delayed he gets a second dose of heparin and is admitted. A full hypercoagulable workup is performed, and it appears that he is deficient in Protein S, is this correct.

First a work-up should never be done on a patient having a thrombotic event. The results may not truly reflect an abnormality. The reality is the patient needs to be treated, whatever the cause. The Protein S deficiency is most likely due to a falsely decreased level due to heparin.

DIAGNOSIS: FALSELY DECREASED PROTEIN S DUE TO HEPARIN

December Case Study

2008-12-01T22:02:00.001-05:00

After a large holiday meal and falling asleep watching television your sedentary, obese cousin wakes up with severe pain in his right calf. He tries to walk off the pain, but it persists. The site is red and hot, clearly inflamed. This continues and it is decided to take him to the hospital. Since it is a holiday the emergency room is very busy, with a skeleton crew.

Upon examination, the resident looks at the situation and suspects a DVT. Since getting imaging will be a while,(due to the holiday) he immediately decides to give the patient a dose of unfractionated heparin.

Several hours after the heparin is given, blood is drawn. Your cousin wants to go home, but they are afraid he will get a PE, so they wait for test results. (It is a holiday...) They give another dose of heparin.

The results were as follows:
PT= 11.4 sec
APTT = 62.8 sec
Fibrinogen = 525
Platelets= 657, 000
D dimer = 786 FEU
APCR = negative
LA = negative
Protein C= 78% (80-120%)
Protein S = 48% (65-135%)

He was admitted due to a Protein S deficiency-
Is this correct, and what is the next course of action?

October Case Study

2008-10-07T08:28:00.001-04:00

A 2 year old boy presents with a cerebral vascular stroke and placed on warafin. He is given 2mg, and presents with an INR 0f 1.5. Despite consistant increase in dosage his INR never exceeds 2.1, the physician wants him to be at an INR of 2.5.
His dosing is 10 times his body weight, and compliance issues are addressed. His mother assures that she is crushing a tablet into applesauce.

What is a possible reason for this?

October Case Study

2008-10-07T08:28:00.000-04:00

A 2 year old boy presents with a cerebral vascular stroke and placed on warafin. He is given 2mg

SEPTEMBER CASE STUDY

2008-09-03T21:54:00.000-04:00

SEPTEMBER CASE STUDY:

A known 3 year old hemophiliac patient has being admitted to a small hospital and need to be transferred to your hospital for a possible treatment. A sample is collected and rushed to the special coagulation laboratory. The APTT is run and the result is > 100 seconds. One point is run to quickly give the pediatric hematologist a result and the 1:10 dilution is 32%. This does not correspond to an APTT of > 100 seconds. The complete results are:
1:20 = 54%
1:40= 75%
1:80=98%

What is a possible explanation for this result? Should this patient receive product, based on the APTT result? What is the factor assay telling us? What test can be done to confirm this?

AUGUST: ANSWERS TO CASE STUDIES

2008-08-18T22:21:00.001-04:00

AUGUST: ANSWERS TO CASE STUDIES:

PT= 12.4 (11.5-13.8)
APTT= 45.7 (28.7-37.2)
APTT 1:1 Mix: 36.2 sec
PNP=29.1 sec

Is this a correction? There are many different definitions to a correction for a mixing study. Some labs use a correction into the normal range, others use within 3 seconds of the PNP. This appears to be a partial correction. It is just 1 second into the normal range, but is 7 second from the PNP. Most labs would look at both an inhibitor and factor assays/
Factor Assays were performed?

Factor Assays:

Factor
1:10
1:20
1:40

VIII
125%
140%
150%

IX
98%
119%
131%

XI
42%
47%
45%

XII
105%
107%
105%

How would this get reported out? The factor XI appears to be decreased, average 45% activity, however, a slight XI inhibitor appears to be present. This could account for the partial correction.
What is the optimum information to provide to the clinician? Since the factor IX is in the normal range, starts at 98% at a 1:10 and increased to 131% at 1:40, calling an inhibitor might be confusing to the clinician, and impact patient care. The factor XI should be reported.
A sample is sent on a 4 month old baby
Two small blue tops are received and the following tests are requested and performed. The results are as follows:

APTT = 68 seconds (25-35 sec)
Factor VIII = 35% at 1:10, 67% at 1:20 and 89% at 1:40
Factor IX = 56% 78% 102
Factor XI = 66 90 110
- Why is it important to know this sample is from a 4 month old baby? Several reasons: babies have different normal ranges, the tubes may be underdrawn, you would want to check for that 9:1 ratio. Another reason is that on a baby samples may be drawn through a line.
- Explain the results of the factor assay and possible causes? The results of all the assays begin in the abnormal range and as the sample is diluted, the value increases. This demonstrates the presence of an inhibitor. Possible causes are heparin or a direct thrombin inhibitor.
- In this situation, what testing should be performed? In this case no clot based assays should be performed.
- Can this sample be saved? If the sample is contaminated with heparin, the sample can be treated with hepzyme and the heparin will be neutralized, and the assays will reflect true levels.
Bleeding or Clotting that is the question?
An 18 year old male has right knee arthroscopy with a diagnosis of hemarthrosis. His own history is insignificant for bleeding, no epistaxis, gum bleeding, non bleeding at circumcision. The family history -- father had a prolonged APTT pre-operatively in his 40's, treated with DDAVP and diagnosed with von Willebrand's disease, grandfather is in his 80's with no history of bleeding, half-sister has a strong history of menorrhagia but is negative for von Willebrand disease.

Physical examination reveals joint laxity.

Coagulation testing results as follows:
PT= 13.7 sec (10.5-13.0)
1:1 mix = 11.2 sec
Control = 11.0 sec
APTT= 33.9 sec (24.5-34.5)
Fibrinogen= 282 mg/dL (180-400)

Fac VII = 33% (50-150%)
Fac 8 = 99% (50-150%)
vWF activity = 59% (50-150%)
vWF antigen = 78% (50-150%)
PFA/ADP = 68 sec (56-128 sec)
PFA/EPI = 139 sec ( 74-186 sec)
- Does this patient have von Willebrand Disease? Most vW workups include a PFA 100, APTT, Factor VIII assay, vW antigen and activity. All assays are normal. This doesn't appear to be von Willebrand disease.
- What is the most obvious diagnosis? Isolated prolonged PT, corrects into normal range and within 0.2 sec of the PNP suggests a factor deficiency. The factor VII is decreased.
- What might be alternative diagnosis? Possible Vitamin K deficiency - II, VII, IX and X
- What is the significance of joint laxity? This can be a characteristic in vascular bleeding disorders.
- What would be the final diagnosis and how would you treat this?Ehler-Danlos syndrome- autosomal dominant, rare connective tissue disorder. Bleeding is variable, it can range from petechiae, purpura, GI bleeds and might even be severe enough to suggest hemophilia.

Donna Castellone,
MS, MT(ASCP)SH

BLEEDING OR CLOTTING THAT IS THE QUESTION?

2008-07-10T14:33:00.000-04:00

Patient presents in the laboratory with the following results in the absence of clinical history:

PT= 12.4 (11.5-13.8)
APTT= 45.7 (28.7-37.2)
APTT 1:1 Mix: 36.2 sec
PNP=29.1 sec

Is this a correction?
Factor Assays were performed?

Factor Assays:

Factor	1:10	1:20	1:40
VIII	125%	140%	150%
IX	98%	119%	131%
XI	42%	47%	45%
XII	105%	107%	105%

How would this get reported out?
What is the optimum information to provide to the clinician?

A sample is sent on a 4 month old baby

2008-06-04T15:47:00.000-04:00

Two small blue tops are received and the following tests are requested and performed. The results are as follows:

APTT = 68 seconds (25-35 sec)
Factor VIII = 35% at 1:10, 67% at 1:20 and 89% at 1:40
Factor IX = 56% 78% 102
Factor XI = 66 90 110

Why is it important to know this sample is from a 4 month old baby?
Explain the results of the factor assay and possible causes?
In this situation, what testing should be performed?
Can this sample be saved?

Bleeding or Clotting that is the question?

2008-05-02T16:40:00.001-04:00

An 18 year old male has right knee arthroscopy with a diagnosis of hemarthrosis. His own history is insignificant for bleeding, no epistaxis, gum bleeding, non bleeding at circumcision. The family history -- father had a prolonged APTT pre-operatively in his 40's, treated with DDAVP and diagnosed with von Willebrand's disease, grandfather is in his 80's with no history of bleeding, half-sister has a strong history of menorrhagia but is negative for von Willebrand disease.

Physical examination reveals joint laxity.

Coagulation testing results as follows:
PT= 13.7 sec (10.5-13.0)
1:1 mix = 11.2 sec
Control = 11.0 sec
APTT= 33.9 sec (24.5-34.5)
Fibrinogen= 282 mg/dL (180-400)

Fac VII = 33% (50-150%)
Fac 8 = 99% (50-150%)
vWF activity = 59% (50-150%)
vWF antigen = 78% (50-150%)
PFA/ADP = 68 sec (56-128 sec)
PFA/EPI = 139 sec ( 74-186 sec)

Does this patient have von Willebrand Disease?
What is the most obvious diagnosis?
What might be alternative diagnosis?
What is the significance of joint laxity?
What would be the final diagnosis and how would you treat this?