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A Practical Guide to Laboratory Haemostasis
 

Data Interpretation: Miscellaneous Tests


Introduction

This section covers many of the tests that were outlined in the section on 'Miscellaneous tests' - some questions do cross over into some of the other sections.

Question 1

You are provided with prothrombin times using two different thromboplastins on a number of patients stably anticoagulated on warfarin as well as several normal healthy individuals.
One thromboplastin is the WHO rabbit reference material and the other is an 'in-house' rabbit material you have prepared in your laboratory.

Plasma Sample PT [s] WHO Reference Preparation PT [s] In-House Preparation
1 32 15.5
2 46 16
3 50 19.5
4 46 16
5 15 12
6 43 16
7 13 12
8 45 18.5
9 32 15.5
10 13 11
11 55 18
12 48 17
13 13 11
14 14 12
15 55 18
16 55 20
17 29 15

A. What is the ISI of the home made material?
B. Would you use this thromboplastin in your laboratory? If not, why not?


Question 2

From the data shown in the attached graph derive the ISI (roughly) for thromboplastin. If you click HERE you can open the graph in a new window.
The WHO Reference thromboplastin has an ISI of 1.0. Points A, B and C are designed to help you.



Using the ISI that you dreive from this graph, what are the INRs of the following samples:

Sample PT INR
1 13s  
2 23s  
3 35s  
4 18s  
5 67s  
Reference plasma 13s  


Question 3
A 20-year-old woman is 32/40 weeks pregnant. She attends the antenatal clinic for a routine check up. You are asked to see her because of the following results:

Test Patient Reference Range
Hb 10.1g/dL 11.5-13.5 g/dL
WCC 6.2 x 109/L 6 - 10 x 109/L
Platelets 80 x 109/L 150-400 x 109/L
MPV 13.1 fL 7.5-9.2 fL

1. What would you do immediately and what investigations would you request?
2. What are the possible diagnoses?

Click here for Part 2

1. You request:
a. A platelet count using citrate as an anticoagulant - the platelet count is 78 x 109/L.
b. A blood film is reported as normal and in particular no platelet clumps are seen.
c. A screen for anti-phospholipid antibodies is negative.
d. The ANA is positive and the ENA shows the presence of Anti-Ro and Anti-La antibodies.

What will you do next?

 

Click here for Part 3

At 36 weeks the platelet count is 62 x 109/L.
What advice will you give to the obstetricians and the obstetric anaesthetists?


Question 4

A 23-year-old man is investigated for a possible bleeding disorder whilst living in Paris. He has a bleeding time performed and this is found to be significantly prolonged at 26 minutes (NR: <10 minutes). He returns to the UK and seeks your advice as to the significance of the prolonged Bleeding Time.

a. Briefly outline the principles of the bleeding time
b. What abnormalities would explain the prolonged bleeding time?
c. What additional tests would you request?
d. Is this test still commonly performed?

Click here for Part 2

1. You decide not to repeat the BT but he scores highly on a structured bleeding questionnaire. You request some additional investigations which show:

Test Patient Reference Range
PT 11.2 11-14s
APTT 51s 23-35s
FVIII:C 0.12 IU/mL 0.5 - 1.5 IU/mL
VWF:Ag 0.11 IU/mL 0.5 - 1.5 IU/mL
VWF:RCo 0.12 IU/mL 0.5 - 1.5 IU/mL

1. What is the diagnosis?
2. Does this explain the prolonged bleeding time?
3. What is French for the Bleeding Time?


Question 5

Briefly explain the principles of the Activated Clotting Time and the Thrombin Time

1. What factors can affect the ACT?
2. What factors can affect the thrombin time?
2. Why do we use the ACT and not the thrombin time to monitor patients on cardio-pulmonary bypass?


Question 6

A 64-year-old man undergoes an aortic valve replacement. Prior to coming off bypass he is given protamine sulphate to reverse the unfractionated heparin. His BP falls and he becomes profoundly hypotensive.

1. What is protamine sulphate and how does it work?
2. What do you think might have happened?


Question 7
A 56-year-old man with a long history of COPD is admitted for surgery.
His pre-operative investigations show a Hb of 19g/dL and an Hct of 0.58 .

Test Patient Reference Range
PT 20s 11-14s
APTT 47s 23-35s

1. What might explain these findings and what would you do next?


Question 8
Outline the mechanism of action of tranexamic acid and DDAVP.


Question 9
A 45-year-old female presents with a spontaneous proximal DVT. She is anticoagulated with initially a low molecular weight heparin and subsequently warfarin with a target INR of 2.5.

Shortly after starting warfarin she complains of bruising and presents 5 weeks later to Accident and Emergency with a large haematoma in her right calf. Her investigations on admission are shown below:


Test Patient Reference Range
INR 2.3 1.0
APTT 117s 28-34.5s
Fibrinogen (Clauss) 3.9 g/dL 2-4 g/dL
Haemoglobin 12.2g/dl 13.5-16.2 g/L
Platelets 298 x 109/L 150-400 x 109/L

1. What additional tests might you request and why?

Click here for Part 2


1. You request some factor assays:

Test Patient Reference Range
FVII 20 u/dL 50 - 150 u/dL
FIX <1 u/dL 50 - 150 u/dL
FX 23 u/dL 50 - 150 u/dL
FV 112 u/dL 50 - 150 u/dL

What do you think may provide an explanation for these findings?

 

Click here for Part 3


Sequence analysis of the F9 gene in this patient identifies a mutation at position Ala-10 within the propeptide for FIX.
1. Comment upon these findings.
2. How would you manage this patient?


Question 10
A 67-year-old man with no previous history of note requires an aortic valve replacement. He has a pre-operative screen performed and this shows the following:

Test Patient Reference Range
PT 13s 11-14s
APTT >120s 28-34.5s
Fibrinogen (Clauss) 3.9 g/dL 2-4 g/L
Thrombin Time 14s 11.5-13.5s
Platelets 358 x 109/L 150-400 x 109/L

1. What would you do next?

Click here for Part 2


1. On a structured bleeding questionnaire he scores 0. He has undergone a number of dental procedures with no problems.
2. Factor VIII, IX and XI assays are normal. What is the most likely diagnosis?

 

Click here for Part 3


He has a Factor XII <1 IU/dl. The cardiac surgeons ask what treatment he needs for his severe Factor XII deficiency and the cardiac anaesthetists ask you how they will manage heparinisation when he goes onto bypass and can they use the ACT to monitor the dosing of heparin?
How will you respond to these questions?


Question 11
A 56-year-old woman is admitted thorough Accident and Emergency having been found confused at home by her partner.

Investigations show:

Test Patient Reference Range
PT 14s 11-14s
APTT 35s 28-34.5s
Fibrinogen (Clauss) 2.1 g/dL 2-4 g/L
Thrombin Time 14s 11.5-13.5s
Hb 8.6 g/dL 7.3 g/dL
Platelets 23 x 109/L 150-400 x 109/L
WCC 11.2 x 109/L 6-10 x 109/L
LDH 2342 U/L <450 U/L
Serum creatinine 356 µmol/L 52-90 µmol/L

1. What additional tests would you request?

Click here for Part 2


1. You request a blood film which is shown below:


What is the most likely diagnosis?
What additional questions might you ask this woman or her family?

 

Click here for Part 3

1. The diagnosis is TTP.

What tests might you request to support this diagnosis?

 

Click here for Part 4

You request ADAMTS 13 studies. Comment upon the results of the tests which are shown below>:

Test Patient Reference Range
ADAMTS 13 Activity <5% 66–126%
IgG Anti-ADAMTS13 85% <4.2%



Question 12
A 45-year-old woman is on treatment for pulmonary TB and develops a large abdominal haematoma. Laboratory investigations show:

Test Patient Reference Range
PT 14s 11-14s
APTT 35s 28-34.5s
Fibrinogen (Clauss) 4.2 g/L 2-4 g/L
Thrombin Time 13s 11.5-13.5s
Platelets 387 x 109/L 150-400 x 109/L
PFA-100 [Collagen:ADP] Normal closure times  

1. What additional tests would you request?

Click here for Part 2

You request a factor XIII screen. Shown below are the results of a FXIII screening test using 5M urea.

Patient: Clot lysis in 45 minutes
Patient Plasma + normal plasma [50:50 mix] No clot lysis after 24 hours
Control plasma No clot lysis after 24 hours


What does this suggest and what is the cause of this?


Question 13
A 67-year-old male is admitted to CCU with unstable angina. He undergoes an emergency coronary angioplasty and receives in addition to 5000 units of unfractionated heparin, Abciximab to prevent re-occlusion of the coronary artery. 3 days after the procedure he is noted to be bruising and his platelets are found to be 5 x 109/L having been 189 x 109/L at the time of his admission.

i. What are you going to do
ii. What do you think has happened
iii. What is Abciximab


Question 14
A 23-year-old man is referred for investigation of prolonged bleeding after dental extraction. Shown below are the results of his premilinary tests. Comment upon the results of these tests and suggest other other that you think would be of value.

Test Patient Reference Range
PT 11s 11-14s
APTT 45s 28-34.5s
Fibrinogen (Clauss) 3.8 g/L 2-4 g/L
Thrombin Time 13s 11.5-13.5s
Platelets 387 x 109/L 150-400 x 109/L
PFA-100 [Collagen:ADP] 155s 60-133s

1. What additional tests would you request?

Click HERE for Part 2
On the basis of the prolonged APTT you request the following Factor Assays:

Test Patient Reference Range
FVIII 16 u/dL 57 - 141 u/dL
VWF:Ag 40 u/dL 50 - 150 u/dL
VWF:Act 31 u/dL 50 - 150 u/dL
RIPA [0.5mg/ml] Absent Absent

What do you think may provide an explanation for these findings?

 

Click HERE for Part 3

You request genetic tests and these show:

1. MLPA [Multiplex ligation independent probe amplification] - heterozygous gene deletion of exons 17-52 of the VWF gene.
2. Heterozygous single base change leading to a p.Arg854Gln mutation [Exon 20.] The latter has been reported in several cases of 2N VWD.

Comments upon the results of these genetic tests. Do they provide an explanation for the observed phenotype.

 


Question 14
A 47-year-old man is see in the Emergency Department with a 2 week history of easy bruising and more recently of a prolonged epistaxis. His past medical history was unremarkable, he had not commenced any new drugs and there was no family history of note.

He had a full blood count performed together with the results of some 'basic' clotting tests. Shown below are the results of his preliminary tests.

Comment upon the results of these tests and suggest other investigations that you think would be of value in reaching a diagnosis.

Test Patient Reference Range
PT 15.9s 11-14s
APTT 21.3s 28-34.5s
Fibrinogen (Clauss) 0.6 g/L 2-4 g/L
D Dimer >60,000 ng/mL 0-230 ng/mL
Platelets 14 x 109/L 150-400 x 109/L
Hb 7.2 g/L 11.5 -15.5 g/dL
WCC 276 x 109/L 5-16 x 109/L

1. What additional tests would you request?

Click HERE for Part 2
You are concerned about the FBC and request a blood film - these are shown below:





Comment upon the results of the blood films?

Why do patients with this particular problem bleed?




Click HERE for the Answers

Try to avoid looking at the answers until you have worked through the questions.

Comments

1. You will gain maximum educational value if you work through each part of each answer before you look at the second and subsequent parts or indeed the answers.

2. The answers will give you some help as to the reasoning behind some of the questions.

3. The questions span disorders from common to exceptionally rare but interesting.

References

 

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Updated: 29-Apr-2012