Clotting disorders Flashcards
(55 cards)
1
Q
How do we test for a factor deficiency or the presence of a coagulation factor inhibitor?
A
50/50 mixture study of patient/normal plasma
corrects - deficiency
no correction - inhibitor
2
Q
How should you approach history-taking with regards to abnormal bleeding?
A
- Emphasis on family history
- Ask about siblings and parents, parents’ siblings
- Particular emphasis on males - X linked disorders
- Unusually severe injuries
- Anaemia?
3
Q
What tests should be ordered when investigating abnormal bleeding?
A
- Full blood count
- Clotting tests
4
Q
Which clotting factors affect one’s APTT?
A
APTT:
- VIII
- IX
- XII
- Von Willebrand factor
5
Q
Which factor deficiencies are seen in Haemophilia?
A
Haemophilia A - Factor VIII
Haemophilia B - Factor IX
6
Q
What is the treatment for Haemophilia?
A
LIFE THREATENING BLEED:
1st line:
- Factor concentrate (replacement)
+ supportive care and subspeciality consultations
- Antifibrinolytic agent
2nd line:
- Bypassing agent (recombinant factor VIIa or VIII inhibitor bypassing fraction)
+ supportive care and subspecialty consultations
- Antifibrinolytic agent
If patient has high titre factor inhibitor, 1st line starts with bypassing agent
NON-LIFE-THREATENING BLEED (into joint/muscle)
1st line:
- Factor concentrate
- Analgesics + physiotherapy evaluation
- Orthopaedic + pain team evaluation
2nd line:
- Bypassing agent
- Analgesics + physiotherapy evsluation
- Orthopaedic + pain team evaluation
If patient has high titre factor inhibitor, 1st line starts with bypassing agent
7
Q
How are the intrinsic and extrinsic factors started?
A
Intrinsic:
- Pre-Kallikrein (PK) and high molecular weight Kininongen (HK) activate factors XI and XII to activate the intrinsic system
- Factors XI, XII and IV all activate factor Xa, which is the centre of the coagulation cascade
Extrinsic:
- Tissue factor (TF) is extruded from damaged endothelial cells of vessel walls
- This activates factor VII to initiate the extrinsic system
- Xa forms thrombin, causing fibrinogen to create fibrin, creating a flot
- The plasmin/plasminogen system is then activated to dissolve the clot
8
Q
What is the extrinsic pathway?
A
Extrinsic:
- Tissue factor -> VIIa -> Xa
Measured by prothrombin time (PT)
9
Q
What is the instrinsic pathway?
A
Intrinsic:
- IX-XII -> VIIIa -> Xa
Measured by APTT
10
Q
What is the common pathway?
A
Common:
Xa -> Thrombin
- Msasured by thrombin time (TT) and PT and APTT
Often just measure Fibrinogen (I)
11
Q
What may cause an isolated prolonged prothrombin time?
A
- Warfarin**
- Factor II
- Factor V
- Factor VII**
- Factor X
12
Q
What may cause an isolated prolonged APTT?
A
- Heparin**
- Factor VIII
- Factor IX
- Factor XI
- Factor XII (but no bleeding)**
- Von Willebrand’s disease
(In types I and II the APTT is often normal)
13
Q
What can cause both the PT and APTT to be prolonged?
A
- Vitamin K deficiency
- Disseminated intravascular coagulation (DIC)
- Heparin toxicity
- Severe factor V or Xa deficiency
(Fibrinogen levels may be normal here!)
14
Q
What is the diagnostic triad?
A
Personal history of bleeding:
- Bruising, often lumpy or unexpected
- Epistaxis: duration 30+ minutes and frequency
- GI tract: start at mouth and work down
- Menses: duration, flooding/clots, number of pads/tampons
- Urine: haematuria
Family history of bleeding:
- Known bleeding disorders
- Bleeding in family members (surgery/dentistry)
- Details of testing: where, by whom, when
Surgical history
Dental history
Cuts and injuries
15
Q
What diagnostic tests are used in clotting disorders?
A
Platelet tests:
- FBC
- Microscopy
- PFA (screen of platelet function)
Specialist tests
- Aggregation and nucleotide release
- Glycoproteins
- Molecular genetics: MYH9
- Bone marrow:- consumption vs production
16
Q
How can we use microscopy to diagnose clotting disorders?
A
Microscopy:
- Large platelets: Bernard Xoulier Syndrome
- Small platelets: Wiskott Aldrich syndrome
- Neutrophil inclusions: MAy Hegglin Anomaly
- Platelet inclusions: Paris Trosseau/Jacobsen’s
17
Q
What are tests of coagulation?
A
- Prothrombin time (PT)
- Activated Partial thromboplastin time (APTT)
- Thrombin time (TT)
- Fibrinogen (Clauss)
- The 50/50 mixture test
18
Q
How do we test clot stability?
A
- Euglobin Clot lysis
1. Make clot on orange stick
2. Leave in fridge for 24hr
3. Check if clot still there - Factor XIII assay
PAI-D: Amish/Chinese
19
Q
What are the basic principles for haemophilia treatment?
A
- Treatment centre/multidisciplinary
- Treat early
- Fast track triage in A&E
- Do not wait for clinical signs to develop
- Take care of veins
- Avoid aspirin and similar drugs (causes platelet disorders)
- Early home therapy
20
Q
What should be the first step in haemophilia treatment?
A
RICE
Rest, ice compression, elevation
There is a tendency to think the only therapy requires id the coagulation factor
21
Q
What is the formula for the amount of factor needed in Haemophilia A?
A
Factor VIII: recombinant, large molecule
Amount needed = (Rise x weight)/2
Half life = 8 hours: give 1-3x daily
22
Q
What is the formula for the amount of factor needed in Haemophilia B?
A
Factor IX: recombinant, small molecule
Amount needed = Rise x weight
Half life 18-24 hours so give once daily
23
Q
How is desmopressin used in clotting disorders?
A
Desmopressin (DDAVP):
Releases stored factor VIII so is useful for mild haemophiliacs
Raises VIII by 2-3x, test with a trial run as variable effects
SC, IV, or intranasal (IN)
24
Q
How is tranexamic acid used in the treatment of clotting disorders?
A
Used in both haemophilia A and B
An anti-fibrinolytic, given orally
Also used in von Willebrand’s during menses?
25
How is home therapy used in haemophilia?
Home therapy
- Parent/carer learns to inject when child is 2yrs
- Patient learns at age 11
- Very convenient
- Very effective
- Saves many hospital visits
26
What is vol Willebrand's disease?
von Willebrand's
- Commonest coagulopathy
- 0.5% of population
- Mucocutaneous bleeding
- Accounts for 15% of menorrhagia
- There are 2 types
- Can be difficult to diagnose (especially type 1)
1. Bleeding history
2. Positive family history
3. Laboratory tests
27
What are the different types of von Willebrand's disease?
Type 1
- Reduced amount of normal vW protein
Type 2
- Abnormal vW protein (IIb overactive)
Type3
- Little or no vW
28
How do we test for von Willebrand's disease?
von Willebrand's screen:
- Factor VIII (normal range 50-150iu/dl)
- von Willebrand antigen (normal range 50-150iu/dl)
- von Willebrand activity (normal range 50-150iu/dl)
Types 1 and 2 are differentiated by using the vWF activity:vWF antigen ratio
if the ratio is >0.6 = type 1
if the ratio is <0.6 = type 2
29
How does type 1 von Willebrand's disease present?
Type 1
- Mild disease
- Bruising/mucosal bleeding
- Menorrhagia
- Operations - dental extractions
30
How does type 2 von Willebrand's disease present?
Type 2
- Mild disease
- Bruising/mucosal bleeding
- Menorrhagia
- Operations - dental extractions
Watch for 2b:
- Overactive protein
- Can result in thrombocytopaenia
- Avoid DDAVP (desmopressin)
- Use vWF concentrate
31
How does type 3 von Willebrand's disease present?
Type 3:
- Severe illness
- Serious mucosal bleeding
- Operative treatment will cause severe bleeding
32
What are the treatments for the different types of von Willebrand's disease?
Type 1: quantitative deficiency
- DDAVP + tranexamic acid
- Watch for diminishing returns in major surgery, vWFactor may be needed
Type 2: qualitative deficiency
under active OR over active (2b)
- vWFactor/DDAVP (avoid in 2b)
Type 3: absent vW factor
- vWFactor
33
What is a venous thromboembolism?
Most VTE occur in the deep veins of the leg
- Normally contraction of the calf muscles squeezed blood up the deep veins of the leg
- Internal valves prevent backflow
In varicose veins etc:
- This mechanism does not work, there is backwash of blood
- Veins bulge and blood pools in the deep veins
34
What is the epidemiology of VTE?
- 25,000 deaths per year
- More than annual death toll from RTA, HIV and breast cancer
- Major avoidable cause of death in modern medicine
- 66% DVT, 33% PE
- Causes 10% of hospital deaths, most are sudden and unexpected`
35
What is Virchow's triad?
Triad of risk factors learning to VTE
- All hospitalised patient need to be considered at risk
- Immobile (in bed)
- Often hypercoagulable (acute phase reactant proteins include fibrinogen, factor VIII and vWF
- Endothelial injury (previous leg or pelvic operation, post operative plaster cast)
1. Stasis of blood flow
2. Endothelial inury
3. Hypercoagulability
36
Who is at risk of VTE?
- Any surgical patient
- Anaesthesia leads to immobility, stasis and reduced blood flow in the legs
- Post-operative period with bed rest - increased risk with increased duration
- Acute reactants post-surgery
- Open surgery greater risk that laparoscopic
!!Medical patients make up the majority of hospital VTE deaths!!
All adult patients (18+) undergo a formal assessment of VTE risk
37
How do we prevent VTE?
- Risk assess each patient (Wells score)
- Early ambulation for all
1. Mechanical:
- Anti-embolism stockings
- Intermittent pneumatic compression sleeves
- Cheap
- Do not affect cogaulation system
- Poor compliance with optimum fitting
- May exacerbate pre-existing arterial insufficiency
- Less effective than pharmacological management
2. Pharmacological:
- Low dose low molecular weight heparin (sc)
- Low dose unfractionated heparin (iv)
- Direct anti-Xa and antithrombin drugs (po)
- Effective
- Know that dose has been given
- Cost!!
- Risk of bleeding
- Allergies and heparin induced thrombocytopaenia and thrombosis (HITT)
Do not use warfarin - intensity of anticoagulation is less predictable and erratic bleeding risk higher than hepatin or DOAC
38
How do we manage acute VTE?
- If suspected according to clinical signs and wells scores then treat immediately
- Do not investigate first unless this can be done within 1 hour for PE or 4 hours for DVT
- Use heparin (LMWH) but sometimes post op use unfractionated (UFH) as it can be immediately reversed if further surgery required
- At the same time as starting heparin, start oral warfarin
- Takes 48-72 hours to reach its therapeutic range at which time the heparin can be discontinued
39
What are thrombi and emboli?
Thrombus:
- A clot within the body
Embolus:
- Some material which is transported in the blood stream and lodges in a blood vessel at a different site
- Can be gaseous, e.g. an air bubble, or solid, e.g. part of a thrombus
- When it impedes or blocks blood flow in the artery it causes an embolism, the consequences of which are infarction of the tissue supplied by the artery
- The bigger the embolus the bigger the artery it blocks and the bigger the area of infarction
40
What is a pulmonary embolism?
- When a thrombus travels up venous circulation
- Enters right atrium, then right ventricle
- Then into the pulmonary arteryies
- Lodges and blocks the artery
A 'massive' pulmonary embolism is when the flow of blood to the right side of the heart is blocked
- Results in a cardiac arrest
41
How does a DVT present?
- Unilateral swollen leg
- Warm
- Calf tenderness, worth with dorsiflexion (Homan's sign)
- Calf circumference more than 3mm wider than the other leg
- Measure 10cm from tibial tuberosity
42
What are some common differential diagnoses for a DVT?
- Cellulitis
- Ruptured baker's cyst
- Muscle haematoma
43
What are the risk factors for a DVT?
- 60+
- Overweight
- Smoking
- Previous DVT
- Take the combined pill or HRT
- Cancer
- Heart failure
- Varicose veins
- Hospital stay
- Bedbound
- Long journeys (3+hrs)
- Pregnancy
- Dehydration
44
What are the signs and symptoms of a PE?
- Chest pain, sometimes upper back
- Difficulty breathing
- Sharp pain (pleuritic)
- Sudden onset
- Shortness of breath
- Coughing up blood
45
What signs of PE are seen on examination?
- Increased respiratory rate
- Tachyarrhythmias (usually sinus tachy but can be AF)
- Signs of DVT
46
What would be seen on an ECG that could suggest a PE?
- Sinus tachycardia
- Possibly atrial fibrillation
- Evidence of right heart strain (right axis deviation/RBBB)
- S1Q3T3 pattern
(numbers indicate leads)
- T wave inversion on lead 3
47
What would be seen on an ABG that could indicate a PE?
- Hypoxia
| - Type 1 respiratory failure (low oxygen, normal or low CO2)
48
How should we use the Wells score and D-Dimer test?
- If Wells score is 'low clinical probability', do a D-Dimer
- If D-Dimer is then negative/normal range, we can exclude a VTE because it is highly sensitive (but not specific)
- If Wells score is 'low clinical probability' and D-Dimer is positive (raised), then do further imaging
- Imaging is usually US doppler of the leg for DVT
- Or CT pulmonary angiogram (CTPA) for a pulmonary embolism
Both of these tests are highly specific
- If Wells score is 'high clinical probability' then go straight for imaging tests
NOTE: these recommendations are not used for pregnant women, hospitals will have local guidelines for pregnancy
49
What is the PERC rule?
```
Rules out PE if no criteria are present and pre-test probability is less than 16%
If any of the following are positive, the PERc rule cannot be used to rule out a PE
- Age 50+
- HR 100+
- O2 sats on air are less than 95%
- Unilateral leg swelling
- Haemoptysis
- Recent surgery or trauma
- Prior PE or DVT
- Hormone use (combined pill, HRT)
```
All of the above add 1 point each
50
What is the threshold of the Wells score?
More than 4 points = PE likely
| Fewer than 4 points = PE unlikely
51
What should be the initial investigations for patients who present with signs of PE?
- ABCDE
- General medical history
- Physical examination
- Chest x-ray to exclude other causes
- Assess PERC/Wells score
52
What treatment is given to patients with a DVT or PE?
- FBC, U&Es, PT and APTT
- Start anticoagulation before results available
- Review and act on results in 24 hours
No renal impairment/active cancer/antiphospholipid syndrome:
- Apixaban or Rivaroaxavan
- Alternative: LMWH 5 days followed by dabigatran or edoxaban
- Offer LMWH and a VKA for at least 5 days or INR is 2.0 on 2 consecutive readings
Renal impairment:
- CrCl 15-50 ml.min, offer apixaban, rivaroaxaban, or LMWH for 5 days followed by edoxaban or dibagatran
- CrCl less than 15ml/min, offer LMWH, UFH
- Offer LMWH and a VKA for at least 5 days or INR is 2.0 on 2 consecutive readings
Active cancer:
- Consider a DOAC
- If not suitable consider LMWH
- Offer LMWH and a VKA for at least 5 days or INR is 2.0 on 2 consecutive readings
Offer anticoagulation for 3-6 months, taking into account tumour site, drug interactions, and bleeding risk
Antiphospholipid syndrome:
- Offer LMWH and a VKA for at least 5 days or INR is 2.0 on 2 consecutive readings
53
What is a massive pulmonary embolism?
- Large clot which lodges in the right side of the heart OR in both pulmonary arteries (saddle embolus) OR one of the pulmonary arteries
Present with:
- Syncope
- Shortness of breath
- Haemoptysis
- Sudden sharp chest pain
- Arterial hypotension (systolic less than 100)
- Cardiogenic shock/cardiac arrest
Medical emergency, requires urgent thrombolysis
54
When are anti-embolus stockings contra-indicated?
Intermittent claudication - stockings exacerbate preexisting peripheral arterial disease
55
What should we monitor when a patient is on LMWH for a week or more?
Potassium levels should be monitored when patients take LMWH for longer than 7 days
- Those patients that have diabetes, chronic renal impairment and on medication that can increase potassium levels are more susceptible to hyperkalamia
(eg ACE inhibitors)
