6. Practical approach to Clotting Disorders

Question 1

3 main systems work together in the body to help blood remain liquid;

1. which works to clot the blood
2. which works to dissolve clots
3. which works as natural inhibitors/anticoags

Answer 1

1. intrinsic and extrinsic clotting cascade
2. Plasminogen/plasmin system
3. protein C, protein S, antithrombin III

Question 2

How does the anticoag warfarin work

Answer 2

reduces the vitamin K dependant coat factors making it difficult to form a clot

Question 3

How does heparin work

Answer 3

on antithrombin III by greatly increases its action (completely inhibiting clots)

Question 4

rTPA (recombinant plasminogen activator), how does this work

Answer 4

it allows clots to be busted by increasing plasmin activity

Question 5

Which substances work as natural anticoagulants in the blood

Answer 5

Protein C, protein S and antithrombin

Question 6

What are the common names of the following;
Factor I 
Factor II
Factor III
Factor IV

Answer 6

I is fibrin
II is prothrombin (gets converted into thrombin)
III tissue factor
IV is calcium

Question 7

what factor does vWF bind to in order to stabilise it

Answer 7

factor VIII

Question 8

Practically, what blood test results would you want to order in a patient who you suspect to have a clotting disorder

Answer 8

FBC
PT 
APTT
Fibrinogen 
Platelet count 
50/50% mixture study

Question 9

in a 50/50 mixture study you take a patients plasma and mix it with 50% of normal plasma
Q: if there is a deficiency, will adding the normal plasma correct the abnormal PT and APTT

Answer 9

yes

Question 10

in a 50/50 mixture study you take a patients plasma and mix it with 50% of normal plasma
Q: if there is an inhibitor present in the patients plasma , will adding the normal plasma correct the abnormal PT and APTT

Answer 10

No

Question 11

If nothing of significance is found on blood results when looking at clotting disorders, what tests would you want to order

Answer 11

Factor essay
vWF tests (VIII, vWF antigen, vWF activity
platelet aggregation and nucleotide release

Question 12

what factor is released from damaged endothelial cells and what factor does it activate to initiate the extrinsic system

Answer 12

Tissue factor (TF) is released which activates factor VII

Question 13

Pre-kallikrein (PK) and high molecular weight kininogen (HK) activate which factors that activate the intrinsic system

Answer 13

factors XI and XII

Question 14

Which pathway causes the prothrombin (PT) time to be increased

Answer 14

the extrinsic pathway which converts TF to VIIIa and Xa

Question 15

which pathway causes the activated partial-thromboplastin (APTT) time to be increased

Answer 15

the intrinsic system which coverts factors IX-XII to VIIIa and Xa

Question 16

if PT and APTT time are both increased then what pathway is it

Answer 16

the common pathway which coverts Xa into thrombin

Question 17

To measure the common pathway what test do you tend to just look at

Answer 17

the level of fibrinogen

Question 18

What abnormalities (ie which factors) should be suspected if the patient has prolonged PT

Answer 18

Warfarin 
II 
V 
VII 
X

Question 19

what abnormalities (ie which factors) should be suspected if the patient has a prolonged APTT

Answer 19

Heparin 
VIII 
IX
XI
XII (but will have no bleeding)
vWD (however in types 1 and 2 APTT is often normal)

Question 20

if both APTT and PT are prolonged then what clinical conditions could this be

Answer 20

vitamin K deficiency (with low fibrinogen) due to liver disease or malabsorption

Disseminated intravascular coagulation (with low fibrinogen), will also see that D-dimers are raised, low platelets and red cell fragments

Heparin toxicity (will have normal fibrinogen)

Rarely you may have deficiencies in factor V or X but will have normal fibrinogen

Question 21

what are the vitamin K dependant factors

Answer 21

II, VII, IX, X

protein C and S

Question 22

What is in the diagnostic triad that a patient will present with if they might have clotting disorders

Answer 22

personal history of bleeding
family history of bleeding
supportive diagnostic tests

Question 23

In the diagnostic triad: People with a personal history of bleeding, what symptoms may they present with

Answer 23

• bruising; unexpected places, no injury, lumpy
• epistaxis (nosebleed): duration and frequency
• GI tract: start at the mouth and wok down
• Menses: duration, flooding/clots, no of pads/tampons
• Urine: haematuria
• Surgical history
• Dental history
• Cuts and injury

Question 24

In the diagnostic triad: describe what would be seen in the family history of bleeding

Answer 24

• if there are known bleeding disorders in the family
• bleeding in family members especially after surgery or dentistry
• if there is, get details of where tested, by whom and when

Question 25

In the diagnostic triad of bleeding disorders: what supportive diagnostic tests would you want to order

Answer 25

platelets (FBC) tests of coagulation (PT, APTT, TT, fibrinogen, 50/50) tests of clot stability (usually done by haematologists such as euglobin clot lysis, factor XIII assay and PAI-D [amish or Chinese])

Question 26

What is the difference between haemophilia A and haemophilia B

Answer 26

A is caused by deficiency in factor VIII | B is caused by deficiency in factor IX

Question 27

what kind of genetic disorder is haemophilia and what does this mean (in terms of demographics)

Answer 27

X linked recessive means men only require one abnormal copy to have the disease if only one copy is affected then they are a carrier commonly only affects males

Question 28

What are the classical features of severe haemophilia

Answer 28

spontaneous bleeding into joints (haemoathrosis) and muscles or any other abnormal bleeding

Question 29

# Fill in the blanks for someone who has severe haemophilia in terms of ; 1. Clotting factor levels in the blood 2. degree of bleeding 3. Frequency of bleeding 4. Site of bleeding

Answer 29

1. less than 1 iu/dl (normal range is 50-150) 2. spontaneous 3. 1-2 X per week 4. Often joint

Question 30

# Fill in the blanks for someone who has moderate haemophilia in terms of ; 1. Clotting factor levels in the blood 2. degree of bleeding 3. Frequency of bleeding 4. Site of bleeding

Answer 30

1. 1iu/dl- 5iu/dl (normal range is 50-150) 2. slight injury 3. 1 X per month 4. less often joint

Question 31

# Fill in the blanks for someone who has mild haemophilia in terms of ; 1. Clotting factor levels in the blood 2. degree of bleeding 3. Frequency of bleeding 4. Site of bleeding

Answer 31

1. more than 5 iu/dl (normal range is 50-150) 2. trauma 3. rare 4. rare

Question 32

What are some of the basic principles for the treatment of haemophilia

Answer 32

treat in tertiary care treat early if in doubt and fast track triage in A&E don't wait for clinical signs to develop take care of veins, treatment Early home therapy (RICE)

Question 33

In haemophilia A what factor is given and what amount and what frequency

Answer 33

``` factor VIII (large molecule) Amount needed= Rise required x weight in kg / 2 1 dose 3 times a day (half life of 8 hours) [ example if have internal knee bleed then raise the levels by 50% whereas if have haemorrhage more like 100% raise] ```

Question 34

in haemophilia B what factor is given and what amount and what frequency

Answer 34

``` Factor IX (small molecule) amount needed = rise x weight (based on clinical situation Once daily (half life is 18-24 hours) ```

Question 35

in which condition would you prescribe desmopressin (DDAVP) and why

Answer 35

Haemophillia A only releases stored factor VIII and so useful for mild haemophiliacs raises VIII by 2-3 times make sure to test this when patient is well to see is suitable

Question 36

in which condition would you prescribe tranexamic acid and why

Answer 36

haemophilia A and B it is an anti-fibrinolytic (oral) slows down the palsminogen/plasmin system which allows blood clots to stay there longer

Question 37

what is the difference between primary and second prophylaxis treatment

Answer 37

primary is where you start to give the missing factors from the age of 18 months - 2 year secondary is where you start treatment after the patient has had 3 joint bleeds

Question 38

for prophylaxis treatment of haemophilia A and B what frequency should the missing factors be given

Answer 38

``` A= factor VIII alternate days but still often 3 times a week B = factor IX can be given 2 times a week ```

Question 39

What is the most common coagulopathy

Answer 39

Von Willebrand disease

Question 40

in terms of vWD 1. what kind of bleeding occurs 2. what percentage of women have menorrhagia (heavy menstrual bleeding) 3. How many types of the disease are there 4. what kind of inheritance

Answer 40

1. mucocutaneous bleeding 2. 15% 3. 3 types 4. autosomal dominant disease

Question 41

What is the difference in classification of the vWF disease types

Answer 41

type 1 - reduction in the amount of normal vWF protein type 2- there is an abnormal vwF protein ( in type 2B it is overactive) type 3- there is little or no vWF protein

Question 42

what would be the treatment for type 1 vWF disease

Answer 42

DDAVP (desmopressin) and tranexamic acid | watching for diminishing returns in major surgery as they may need vWF

Question 43

what would the treatment for type 2 vWF disease be

Answer 43

vWF | not DDAVP in type 2b

Question 44

what would the treatment for type 3 vWF disease be

Answer 44

vWF concentrate | consider prophylaxis and genetic advice

Question 45

what makes up a vWF screen

Answer 45

factor VIII vW antigen vW activity

Question 46

how to do differentiate type 1 and type 2 vWF disease

Answer 46

by using the ratio of vWF activity: vWF antigen ratio greater than 0.6 its type 1 ratio less than 0.6 its type 2

Question 47

why would you use desmopressin (DDAVP)

Answer 47

stimulates the release of vWF

Question 48

What clinical signs would you see in types 1 and 2 of vWF disease

Answer 48

mild brusing bruising/mucosal bleeding menorrhagia operations - dental extractions

Question 49

what is the rare 2B vWF disease

Answer 49

you have an over reactive vWF protein which can result in thrombocytopenia (low levels of platelets)

Question 50

in patients with type 2B vWF disease, why would you use vWF concentrate rather than desmopressin (DDAVP)

Answer 50

desmopressin will release vEF from stores (just in the same way in haemophiliacs it releases stored factor VIII) and of course this will be detrimental

Question 51

What other component in the blood is it important to check in patients who bleed

Answer 51

their iron levels as they will probably have iron deficiency

Question 52

What is the role of vitamin K

Answer 52

regulates blood coagulations by making coagulation factors mature

Question 53

Producing which clotting factors requires an enzyme that uses vitamin K

Answer 53

II, VII, IX and X

Question 54

what kind of vitamin is vitamin K and where is it synthesised

Answer 54

fat soluble and synthesised by bacteria in the gut

Question 55

in platelet plug formation what is the role of vWF

Answer 55

helps bind platelets to the exposed collagen | thromboxane A2 helps with vasospasm and platelet aggregation

Question 56

what converts fibrinogen into fibrin in the clotting cascade

Answer 56

thrombin and calcium

Question 57

how does the blood vessels slow down coagulation (anticoagulation)

Answer 57

protein C and S binds to thrombomodulin which inactivates factors V and vIII antithrombin also binds directly to thrombin so blood clot can't form