Case 6 - Clotting Disorders and VTE Flashcards
What are Haemophilia A and B?
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
What is Von Willebrand’s Disease?
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
What is the physiology of clotting?
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
What are the intrinsic, extrinsic and common clotting pathways?
Intrinsic:
VIII, IX, XI, XII
Heparin and vWF work on this pathway too
Common:
II, V, X
Extrinsic:
VII
Warfarin
What questions should you ask in a clotting history?
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?
What investigations would you perform if you suspect a clotting disorder?
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
What are some platelet disorders?
Large = Bernard Soulier syndrome Small = Wiskott Aldrich syndrome Neutrophil inclusions = May Hegglin Anomaly Platelet inclusions = Pan's Trousseau/Jacobsons
What are factor inhibitors?
At risk in those:
- Severe clotting disorder
- Many transfusions
- Genetic mutation
In 30% of Haemophilia A and 3% of Haemophilia B
What do you need to know when treating a clotting disorder?
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
How do you treat life-threatening bleeds in a patient with a clotting disorder?
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
How do you treat MSK bleeds in a patient with a clotting disorder?
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
How do you treat urinary tract bleeds in a patient with a clotting disorder?
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
How do you treat nasal/oral bleeds in a patient with a clotting disorder?
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
How do you treat the different types of von Willebrands Disease?
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
What is the pathophysiology of a VTE?
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
How does a DVT become a PE?
DVT > piece of clot breaks off >travels through veins of the body > IVC > RA > RV > pulmonary artery > becomes lodged in a pulmonary vessel
What are the RFs for a VTE?
- In hospital
- Infection
- Cancer
- Antiphospholipid syndrome
- Obesity
- Pregnancy
- Recent surgery
- Previous VTE
- Thrombophilia
- Heart/lung disease
- OCP/HRT
- Smoker
- Dehydrated
- Older age
What are signs and symptoms of a DVT?
Red, hot swollen leg
Tender leg, worse on dorsiflexion (homan’s sign)
Unilateral leg swelling
Unilateral pitting oedema
What are signs and symptoms of a PE?
Pleuritic chest pain Signs of DVT SOB Tachycardia Haemoptysis T1RF Tachyarrythmias - S1Q3T3
How do you prevent VTE?
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
How do you diagnose VTE?
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
How do you treat VTE?
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
