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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?

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?

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?

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?

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?

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?

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

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

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?

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

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?

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?

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.

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?

1. What additional assay would you request and why?

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?

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	0.44 IU/mL	0.70 - 1.50 IU/mL

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

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?

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

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?

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?

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?

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?

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?

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?

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?

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?

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?

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?

His vitamin K dependent clotting factors [II, VII, IX & 10 + Proteins C and S are all <5% of normal.]

What does this make you think?

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

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?

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?

In view of the prolonged PT, 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?

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?

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?

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?