Coagulation Case Studies

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?

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?

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:

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

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?

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?
  

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?