Practical-Haemostasis.com

A Practical Guide to Laboratory Haemostasis

 

Data Interpretation: Screening Tests



Introduction

The following questions will allow you to work through a number of scenarios.

Question 1
A 2-year-old girl is brought to your clinic. Developmentally normal, her parents had noticed her to be bruising easily.

Coagulation tests show:

Test Patient Reference Range
PT 13s 11-14s
APTT 105s 23-35s
Fibrinogen (Clauss) 2.7g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s
1. What additional questions might you ask the parents?
2. Briefly outline how you would investigate the clotting abnormalities.
3. What are the possible explanations for these results?

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1. You repeat the tests and confirm the abnormality.
2. The prolonged PT and APTT correct in a mix with normal plasma.

What factor assays would you request and why?


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You request FVIII, IX and XI assays.
The FIX and FXI assays are normal but the FVIII assay is <1 IU/dl.

1. What is your differential diagnosis?
2. What mechanisms might explain this finding?


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1. FV and VWF assays are normal.
2. The chromosomal karyotype is normal
3. What mechanisms might explain the finding of a FVIII:C < 1IU/dL?


Question 2
A 45-year-old man is referred for further investigation following the finding of an abnormal coagulation profile. He had contacted his GP having developed easy bruising and epistaxes. His health had previously been excellent apart from a recent chest infection for which he had been prescribed amoxicillin.

Investigations show:

Test Patient Reference Range
PT 45s 11-14s
APTT 79s 23-35s
Fibrinogen (Clauss) 2.9g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s

1. What are the abnormalities and what do you think are the possible explanations.
2. What additional tests would you request?

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1. You repeat the tests and confirm the abnormality.
2. The prolonged PT and APTT do not correct in a mix with normal plasma.

What factor assays would you request and why?


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You request a FV, FX and FII assay.
The FX and FII assays are normal but the FV assay is 3 IU/dl.

What is your diagnosis and why?


Question 3
A 23-year-old woman presents to her GP with menorrhagia. The GP requests a coagulation screen and the results of this are shown below:

Test Patient Reference Range
PT 34s 11-14s
APTT 82s 23-35s
Fibrinogen (Clauss) 2.6g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s

1. What questions might you ask this lady that would be of relevance?
2. How would you proceed with the investigation of this patient?

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1. This lady is of Iranian origin. Her parents are first cousins.
The only history of note is that she had a brother who died from an intra-cranial bleed shortly after birth.
2. The prolonged PT and APTT correct in a 50:50 mix with normal plasma

Which factor assays would you request and why?

 

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You request a FX assay - the raw data for a PT-based FX assay is shown below:

 
Dilutions
1/10 1/20 1/30 1/40 1/80 1/100 1/1000
Reference plasma 25s   32s     38s 59s
Patient 1
35s
   
  54s
82s

The FX reference standard has a concentration of 100%.

1. What is the diagnosis?
2. What assays are available to measure FX levels in plasma


Question 4
A 45-year-old man presents with an extensive above knee DVT extending into the iliac veins. He is otherwise well with no past medical history of note.

His pre-anticoagulation screen shows:

Test Patient Reference Range
PT 14s 11-14s
APTT >120s 23-35s
Fibrinogen (Clauss) 3.2g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s

1. What is the most likely diagnosis?

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1. The prolonged APTT corrects in a mix with normal plasma.
2. What factor assays would you request?

 

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Factor XII:C <1 IU/dl.
Do you think the low FXII level is clinically important?
If you elect to treat this patient with unfractionated heparin how would you monitor this?


Question 5
A 10-day-old baby, previously well, breast fed and born at home is found by his parents unconscious and bleeding from mouth and gums. The only history of note is that the mother had had a major post-partum haemorrhage and had required emergency admission to hospital.

A coagulation screen shows:

Test Patient Reference Range
PT 102s 11-14s
APTT >120s 23-35s
Fibrinogen (Clauss) 1.9g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s

1. What is the most likely diagnosis?
2. How would you confirm this?
3. Why does this occur?


Question 6
The following results were found in a 32-year-old woman as part of a 'Well Woman Screen.'

Test Patient Reference Range
PT 12s 11-14s
APTT 95s 23-35s
Fibrinogen (Clauss) 3.9g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s

1. List additional tests you would perform following the findings shown above to clarify the diagnosis

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The prolonged APTT corrects in a mix with normal plasma.
What is the most likely diagnosis?


Question 7
What might explain the laboratory findings shown below?

Test Patient Reference Range
PT 65s 11-14s
APTT 75s 23-35s
Fibrinogen (Clauss) 0.8g/L 1.5-4.0g/L
Thrombin Time 47s 10-13s


Question 8
A clotting screen on a woman of Turkish origin shows the following results:


Test Patient Reference Range
PT 35s 11-14s
APTT 56s 23-35s
Fibrinogen (Clauss) 2.8g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s

1. What other tests would you request and why?

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1. The PT and APTT correct in a mix with normal plasma
2. What factor assays would you request?
3. Is this ethnic origin of the lady important?


Question 9
A 56-year-old woman with a suspected carcinoma of the bowel is admitted for surgery. A pre-operative clotting screen shows:

Test Patient Reference Range
PT 14s 11-14s
APTT 76s 23-35s

1. What other tests would you request and why?

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Investigations show the presence of a lupus anticoagulant.
The surgeons are concerned that this lady will bleed during surgery because of this. What will you tell them?


Question 10
A 23-year-old woman develops a DVT. There is no other personal or family history of note. She is not on the oral contraceptive pill.

Test Patient Reference Range
PT 14s 11-14s
APTT 95s 23-35s

1. Comment upon the results of the PT and APTT.
2. What tests would you request next?

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1. Results show the presence of a lupus anticoagulant.
2. Briefly outline the tests you would perform to establish the presence or absence of a lupus anticoagulant.


Question 11
A 53-year-old man is admitted unconscious to casualty. His coagulation results are shown below:

Test Patient Reference Range
PT >120s 11-14s
APTT >120s 23-35s
Fibrinogen (Clauss) 2.01g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s
1. What is the most likely explanation for these findings?

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He has a midline sternotomy scar and has been taking warfarin for many years.
1. How does warfarin work?
2. How do we monitor warfarin and why do we use this test?
3. How would you address the coagulation abnormalities in this patient?


Question 12
Comment upon the following results in an 18-year-old asymptomatic individual who is admitted with acute appendicitis.

Test Patient Reference Range
PT 45s 11-14s
APTT 46s 23-35s
Fibrinogen (Clauss) 0.8g/L 1.5-4.0g/L
Thrombin Time 45s 10-13s
Reptilase Time 51s 11-14s

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1. What additional assay would you request and why?


Question 13
A 28-year-old woman with Crohn's disease is found to have the following clotting abnormalities:

Test Patient Reference Range
PT
50:50 Mix NP
>120s
14.2s
10.6-12.4s

APTT
50:50 Mix NP
105s
27.7s
21-32s

Fibrinogen (Clauss) 1.9g/L 2-4g/L
Inhibitor Screen
 Immediate Mix
 2 hour incubation

29s
28.3s
 
1. What additional tests would you request?

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1. You repeat the tests and confirm the abnormality.
2. You request 50:50 mix correction tests - the results of which are shown below:

Test Patient Reference Range
PT
50:50 Mix NP
>120s
14.2s
10.6-12.4s

APTT
50:50 Mix NP
107s
27.7s
21-32s

Fibrinogen (Clauss) 1.9g/L 2-4g/L

What factor assays would you request and why?

 

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Below are the results of the factor assays you may have requested.

Factor Assay Patient Reference Range
FII <0.01 IU/mL 0.5 - 1.5 IU/mL
FV 1.13 IU/mL 0.5 - 1.5 IU/mL
FVII <0.01 IU/mL 0.63 - 1.71 IU/mL
FIX <0.01 IU/mL 0.55 - 1.58 IU/mL
FX <0.01 IU/mL 0.59 - 1.69 IU/mL
FXI 0.74 IU/mL 0.70 - 1.50 IU/mL

What is the most likely diagnosis?
Why is liver disease an unlikely diagnosis?


Question 14
A 22-year-old man is admitted for an arthroscopy. He has no previous medical history of note but investigations show the following:


Test Patient Reference Range
PT 13s 13.5 -16.5g/dL
APTT >120s 4 - 11 x 109/L
Fibrinogen (Clauss) 2.7g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s
1. What is the most likely diagnosis?

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1. You suspect a contact factor deficiency as there is no history of note but request the following:

Factor VIII, IX, XI and XII assays - Normal .
Lupus anticoagulant screen - Negative.

What is your diagnosis?


Question 15
A 23-year-old woman is 34 weeks pregnant and found to have the following results:

Test Patient Reference Range
Hb 10.9 g/dL 11-14s
WCC 9.7 x 109/L 23-35s
Platelets 98 x 109/L 150 - 400 x 109/L
MCV 94 fL 80 -98fL
MPV 12.1 fL 7.5 - 11.5 fL
1. What do you think the most likely diagnosis is?
2. Are there are additional tests you might request?


Question 16
A 23-year-old woman is 9 weeks pregnant and admitted with a miscarriage. Her investigations show:

Test Patient Reference Range
PT 21s 11-14s
APTT 39s 23-35s
Fibrinogen (Clauss) 0.42g/L 1.5-4.0g/L
Thrombin Time 35s 10-13s
Reptilase Time 43s 11-14s

1. Comment upon the results of these findings.
2. What additional tests would you request?

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1. You suspect DIC but when she has recovered her clotting abnormalities are essentially unchanged. What additional tests might you request?


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You request a Fibrinogen Antigen which is reported as 3.4g/L.
1. What is the diagnosis.
2. What might you consider in a future pregnancy?


Question 17
An 18-year-old woman with nephrotic syndrome is admitted for a renal biopsy. Shown below are the results of a coagulation screen.

Comment upon the results of these tests and what do you think may be the explanation?

Test Patient Reference Range
PT 13s  
APTT 35s  
Fibrinogen (Clauss) 3.8 g/L  
Thrombin Time 23s  
Reptilase Time 25s  

1. Comment upon the results of these findings

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1. These results are consistent with hypo-albuminaemia.
2.How could you confirm that these abnormalities are due to the low albumin?
3. What advice would you give to the nephrologists regarding the risk of bleeding associated with these abnormalities and what pre-biopsy treatment would you advise?


Question 18
A 25-year-old woman is admitted through A & E with a 5-day history of easy bruising. Her admission was precipitated by a grand mal convulsion which she suffered at home.

Test Patient Reference Range
Hb 7.6 g/dL 11.5-13.5g/dL
WCC 11.9 x 109/L 4 -11 x 109/L
Platelets 10 x 109/L 150 - 400 x 109/L
PT 13s 11-14s
APTT 35.6s 23-35s
Fibrinogen 2.1g/L 1.5-4.0g/L

1. What is you differential diagnosis?
2. What additional tests would you request?

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1. A repeat FBC confirms these abnormalities
2. The LDH is elevated at 2389 U/dL
3. The Troponin T is raised
4. The creatinine is raised at 389 µmol/mL
5. A blood film is shown below:



What is the diagnosis?
Are there any additional tests you would request?


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The ADAMTS13 activity results are shown below:

Test Patient Reference Range
ADAMTS13 Activity <5% 66-126%
ADAMTS13 Inhibitor Assay 28 AU/mL <11 AU/mL


What does this suggest?
What are the principles of treatment in this disorder?


Question 19
Briefly outline the roles for the following snake venoms:

Venom Mode of Action
Botrocetin  
Ristocetin  
Russell Viper Venom  
Textarin  
Ecarin  
Botox  
Ancrod  
Protac  
Reptilase  


Question 20
A 3-month old baby is admitted to hospital unconscious. A CT scan shows a large intra-cerebral bleed. The results of clotting tests are shown below:

Test Patient Reference Range
PT 14s 11-14s
APTT 32.8s 23-35s
Fibrinogen 3.1g/L 2-4 g/L
FXIII screen [5M urea] Control: No lysis at 24 hours
Patient: Lysis at 24 hours

1. Comment upon the results of these tests?
2. What questions might you ask the parents?

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1. The parents are first cousins and were born in North Africa.
2, Their first child died shortly after birth from cause unknown. They have two other children with no apparent problems.
3. What additional tests might you request?


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You request a FXIII:B ELISA which shows a value of 110 U/dL [Reference Range: 60-130 U/dL].

Are there any additional tests you would request?


Question 21
A 47-year-old male is admitted for a partial nephrectomy. His pre-operative screen shows:

Test Patient Reference Range
PT 12.5s 11-14s
APTT 42s 23-35s
Fibrinogen 3.4 g/L 2-4g/L
PFA-100 Collagen-ADP Cartridge: Normal closure times  

1. What additional tests would you request?

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1. You request FVIII, FIX, FXI and Von Willebrand Factor assays.

The FVIII assay is 6.2 IU/dL and this confirmed on repeat testing.
VWF Assays [VWF:Ag and VWF:Act] are normal.

2. What is the diagnosis and how would you manage his surgery?



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1. You diagnose mild Haemophilia A and elect to treat him with a recombinant FVIII to cover his surgery rather then DDAVP.

The surgery is uneventful and after 5 days his rFVIII is stopped and he is sent home. He represents some 3 weeks later with widespread subcutaneous bruising on his arms and legs which came on suddenly with no history of trauma.

Investigations show:

Test Patient Reference Range
PT 12.5s  
APTT 133s  
Fibrinogen 3.4 g/L  
FVIII:C < 1 IU/dL  

1. What is the most likely explanation for these findings?



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1.You suspect he has an inhibitor which is confirmed. He has a titre of 12 Bethesda Unit s[Bu]. How will you manage him?

2. If he requires surgery again in 2 years how would you manage him?


Question 22

A 24-year-old student presents to the Emergency Department with a short history of easy bruising and frank haematuria. On examination he has widespread bruises but there is little else to find.
There was no past medical history or family history suggestive of a bleeding disorder.

His blood tests show:

Test Patient Reference Range
PT >120s 11-14s
APTT >120s 23-35s
Fibrinogen (Clauss) 3.2g/L 1.5-4.0g/L
Thrombin Time 13s 10-13s
Hb 8.9 g/dL 11.5-13.5g/dL
Platelets 256 x 109/L 150-400 x 109/L

1. What questions might you ask this student?
2. What are the possible diagnoses?

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1. He does not admit to taking any anticoagulant drugs. His diet is good and he has not been abroad recently>1.
2. The prolonged PT and APTT correct in a mix with normal plasma.
3. What factor assays would you request?

 

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His vitamin K dependent clotting factors [II, VII, IX & X + Proteins C and S are all <5% of normal.]

What does this make you think?

 

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On further questioning he admits that he have 'taken' some rat poison a few days earlier but he is not too sure how much.


Question 23

A 6-year-old boy is brought to the Emergency Department having dropped a book onto his foot and which resulted in a large bruise. His parents commented that he seemed to bruise more easily than other boys of his age and more so that than their other son.

His blood tests show:

Test Patient Reference Range
PT 15.2s 11-14s
APTT 79s 23-35s
Fibrinogen (Clauss) 2.9g/L 1.5-4.0g/L
Thrombin Time 12.1s 10-13s
Platelets 319 x 109/L 150-400 x 109/L

1. What questions might you ask this student?
2. What are the possible diagnoses?

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1. There was no past medical history of note and no family history suggestive of a bleeding disorder. The parents are not related.

2. You request VIII, IX, XI and Von Willebrand Factor assays - the results of which are shown below.

Factor Patient Reference Range Comments
FVIII 0.92 IU/mL 0.57 -1.40 IU/mL Non-parallel
FIX 0.67 IU/mL 0.7 - 1.55 IU/mL Non-parallel
FXI 0.87 IU/mL 0.72 - 1.52 IU/mL Non-parallel
VWF:Ag 0.65 IU/mL 0.53 - 1.49 IU/mL  
VWF:Act 0.63 IU/mL 0.53 - 1.49 IU/mL  


What additional tests would you request and why?

 

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You request a screen for a lupus anticoagulant - the results of which are shown below:

Test Patient Reference Range
dRVVT ratio 2.72 <1.20
Phospholipid Correction 44.5% <15%
SCT ratio 1.78 <1.24
Phospholipid Correction 19.5% <15%

What do you think the diagnosis is?
Are there any additional tests you might request (clearly the answer is yes!!) and why?

 

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In view of the prolonged PT and APTT you request a factor II assay which is: 0.36 IU/mL [Reference Range: 0.53 - 1.38 IU/mL].

What would your final diagnosis be?
Do these findings provide an explanation for the child's history of easy bruising?


Question 24

A 6-month-old boy is admitted to hospital with a short history of vomiting and lethargy which had started 24 hours previously. A CT scan shows evidence of a large subdural haematoma with midline shift.

His blood tests show:

Test Patient Reference Range
PT 38s 11-14s
APTT 109s 23-35s
Fibrinogen (Clauss) 2.9g/L 1.5-4.0g/L
Platelets 160 x 109/L 150-400 x 109/L

1. What questions might you ask the parents?
2. What are the possible diagnoses?

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1. There was no past medical history of note and no family history suggestive of a bleeding disorder.
The parents are first cousins.

2. You request a series of factor assays based upon the PT and APTT data - the results of which are shown below:

Factor Patient Reference Range
FII 0.08 IU/mL 0.57 -1.40 IU/mL
FVII 0.22 IU/mL 0.7 - 1.55 IU/mL
FIX 0.28 IU/mL 0.72 - 1.52 IU/mL
FX 0.15 IU/mL 0.53 - 1.49 IU/mL


What additional tests would you request and why?

 

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You request a factor V assay which is 0.79 IU/mL [Reference Range: 0.57 -1.40 IU/mL].

What would explain these findings?
How would you treat this child?

 

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The child has no evidence of malabsorption and appears well nourished.
Liver function tests are normal.

The parents refuse to allow you to take a blood sample from them to perform any clotting factor assays.

You elect to treat the child with Fresh Frozen Plasma [FFP] + Vitamin K and the clotting factor abnormalities return to normal. However, 3 weeks later the child is noted to be bruising easily and repeat clotting factor assays are similar to those at presentation.

What do you think the diagnosis is?
How will you mange this child in the long-term?
What else might this child show as a consequence of this disorder?


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