Case 6 - Clotting Disorders and VTE

Question 1

What are Haemophilia A and B?

Answer 1

X-linked recessive disorders
Haemophilia A is a FVIII deficiency
Haemophilia B is a FIX deficiency
Graded as mild moderate or severe dependent on factor levels

Question 2

What is Von Willebrand’s Disease?

Answer 2

Can be 3 types
Most common clotting disorder in the UK
Causes menorrhagia and mucocutaneous bleeding

1) not enough vWF - mild
2a) abnormal vWF
b) Overactive vWF > intravascular coagulation and therefore thrombocytopenia. Desmopressin releases vWF from stores and is tehrefore detrimental
3) very little/no vWF - severe

Question 3

What is the physiology of clotting?

Answer 3

The clotting cascade works to form a clot
Inhibited by protein C and S, ATIII
Heparin increases ATIII activity
Warfarin decreases the levels of vitamin K clotting factors (II, VII, IX and X)

There are factors that work to dissolve the clot = plasminogen/plasmin system
Recombinant tPA acts to increase plasmin activity

Question 4

What are the intrinsic, extrinsic and common clotting pathways?

Answer 4

Intrinsic:
VIII, IX, XI, XII
Heparin and vWF work on this pathway too

Common:
II, V, X

Extrinsic:
VII
Warfarin

Question 5

What questions should you ask in a clotting history?

Answer 5

Diagnostic triad is PHx of bleeding, FHx of bleeding and supporting lab tests

Any dental/surgical Hx?
Abnormal menses?
Epistaxis?
GI tract bleeding - work down from mouth
Haematuria
Bruising in unusual areas?
Reaction to normal cuts/injuries
FHx of clotting disorders or abnormal bleeding?
Pattern of FHx?

Question 6

What investigations would you perform if you suspect a clotting disorder?

Answer 6

Platelets - microscopy
PT - extrinsic and common
APTT - intrinsic and common
Fibrinogen
50/50 mixing studies, if there is resolution, this means there's a deficiency, if not it means there is an inhibitor
Factor assays as indicated
vWF specific studies

Question 7

What are some platelet disorders?

Answer 7

Large = Bernard Soulier syndrome
Small = Wiskott Aldrich syndrome
Neutrophil inclusions = May Hegglin Anomaly
Platelet inclusions = Pan's Trousseau/Jacobsons

Question 8

What are factor inhibitors?

Answer 8

At risk in those:

• Severe clotting disorder
• Many transfusions
• Genetic mutation

In 30% of Haemophilia A and 3% of Haemophilia B

Question 9

What do you need to know when treating a clotting disorder?

Answer 9

Type of disorder and severity
Who the patient is being treated under
Factor inhibitor levels
History of bleeding and products used in the past
Anatomical site of the bleed

Question 10

How do you treat life-threatening bleeds in a patient with a clotting disorder?

Answer 10

No inhibitors - ABC and BLS, give factor concentrate, monitor levels

Low inhibitors - give factor concentrate, bypassing agent, tranexamic acid

High inhibitors - give bypassing agent, tranexamic acid

Question 11

How do you treat MSK bleeds in a patient with a clotting disorder?

Answer 11

No inhibitors - RICE, factor concentrate, physio

Low inhibitors - analgesia, factor concentrate, bypassing agent, tranexamic acid, orthopaedics, pain team, physio

High inhibitors - analgesia, bypassing agent, tranexamic acid, orthopaedics, pain team, physio

Question 12

How do you treat urinary tract bleeds in a patient with a clotting disorder?

Answer 12

No inhibitors - fluids, factor concentrate supportive treatment

Low inhibitors - fluids, factor concentrate, bypassing agent, tranexamic acid, supportive treatment

High inhibitors - fluids, bypassing agent, tranexamic acid, supportive treatment

Question 13

How do you treat nasal/oral bleeds in a patient with a clotting disorder?

Answer 13

No inhibitors - desmopressin in mild Hameophilia A, tranexamic acid and factor concentrate

Low inhibitors - tranexamic acid, factor concentrate, bypassing agents

High inhibitors - tranexamic acid, bypassing agents

Question 14

How do you treat the different types of von Willebrands Disease?

Answer 14

1) give vWF factor concentrate, desmopressin if DDAVP test shows response, tranexamic acid
2a) give vWF factor concentrate, desmopressin if DDAVP test shows response
2b) vWF concentrate
3) give vWF factor concentrate, prophylaxis and genetic advice

Question 15

What is the pathophysiology of a VTE?

Answer 15

Needs Virchow’s triad - stasis, endothelial injury and hypercoagulopathy

All hospital patients are at risk of all three

Endothelial injury - due to HTN, infections, toxins, high cholesterol
The subendothelial layer being revealed leads to activation of the clotting cascade
Turbulent blood flow can both cause, and be caused by, endothelial injury

Stasis can also be caused by turbulent blood flow
Increased contact time between platelets and endothelium > activation of cascase

Hypercoagulopathy can be primary ie. disruption of the cascade, or secondary ie. AF etc.
The younger the clot, the easier it is to dissolve e.g. with tPA

Question 16

How does a DVT become a PE?

Answer 16

DVT > piece of clot breaks off >travels through veins of the body > IVC > RA > RV > pulmonary artery > becomes lodged in a pulmonary vessel

Question 17

What are the RFs for a VTE?

Answer 17

• In hospital
• Infection
• Cancer
• Antiphospholipid syndrome
• Obesity
• Pregnancy
• Recent surgery
• Previous VTE
• Thrombophilia
• Heart/lung disease
• OCP/HRT
• Smoker
• Dehydrated
• Older age

Question 18

What are signs and symptoms of a DVT?

Answer 18

Red, hot swollen leg
Tender leg, worse on dorsiflexion (homan’s sign)
Unilateral leg swelling
Unilateral pitting oedema

Question 19

What are signs and symptoms of a PE?

Answer 19

Pleuritic chest pain
Signs of DVT
SOB
Tachycardia
Haemoptysis
T1RF
Tachyarrythmias - S1Q3T3

Question 20

How do you prevent VTE?

Answer 20

Mechanical or pharmacological
Every patient over the age of 18 should be screened for VTE prophylaxis upon entry to the hospital

Mechanical could include TEDS etc, these are cheap and do not interfere with the clotting cascade
However, they are contrainidcated in intermitterent claudication, and you cannot guarantee the compliance
May exacerbate arterial insufficiency
Less effective

DOACs/LMWH/UFH are more effective and complicance is increased
However, they interfere with the clotting cascade and there may be risk of anaphylaxis and bleeds

Question 21

How do you diagnose VTE?

Answer 21

2 level Wells score
If >4 PE, >2 DVT, means it is likely
Perform the appropriate scan - doppler US, or CTPA, or if these can’t be done within 1 hour for PE and 4 hours for DVT, treat
If not, do D-dimer, if this cannot exclude VTE, perform the scan anyway

Question 22

How do you treat VTE?

Answer 22

LMWH in those who are stable
UFH in those with renal failure and who are not haemodynamically stable - reversible with protamine

Should also start warfarin
This takes 72 hours to get to therapeutic window
Can stop heparin when INR 2 or for 5 days
On warfarin for 3 months, then reassess

Thrombolytics may be considered in low risk DVT patients or haemodynamically unstable with a PE e.g. urokinase