Case 8: VTE, bleeding disorders Flashcards
1
Q
Unfractionated heparin
A
- Indictions: acute treatment an prophylaxis of thromboembolic disorders
- MoA: Complexes and potentiates the action of AT which binds to free circulating serine proteases IIa, Xa, IXa, and Xia (Predominantly inhibits IIa and Xa)
- Dosing: acute treatment requires IV bolus
- Monitoring: assess heparin level 4-6 hours after starting treatment or dose adjustment. FBC on day 7 or day 3 if exposure to heparin within 3 months
2
Q
Low molecular weight heparin (LMWH)
A
- Indications: Treatment and prophylaxis of thromboembolic disease. LMWH preferred over UFH as first line agent unless renal function inadequate or acute anticoagulant control required
- MoA: same as UFH but has a higher ratio of anti-Xa to anti-IIa activity
- Dosing: dont need bolus. SC injection into roll of abdominal fat not within 2 inches of the umbilicus
- Use with caution if CrCl <20-20ml/minute
- Monitoring: baseline FBC and CrCl. Monitoring not needed except obesity, renal dysfunction, unexplained bleeding
3
Q
Warfarin
A
- Common indications: prevention of stroke in A-fib, long term secondary prevention of venous thromboembolism, prevention of thrombosis in mechanical heart valve
- MoA: Inhibits Vitamin K epoxide reductase leading to lower vitamin K dependent clotting factors (Factors II, VII, IX, X, Protein S and C)
- Metabolism: Hepatic CYP450
- Common dosing: Start at 5 mg PO OD and adjust as per INR. Administer at the same time, once a day
- Risks: warfarin toe necrosis, ‘purple toe’ syndrpme, teratogenic
4
Q
Warfarin monitoring and INR
A
- Monitoring: check INR frequently (days-weeks) whilst titrating until stable dose
- Target INR 2-3 for treatment and prevention of thromboembolic events
- INR 2.5-3.5 is required for patients with mechanical mitral valve
5
Q
Apixaban
A
- Acute and long term anticoagulation for VTE, thromboprophylaxis for VTE (i.e. elective hip or knee replacement surgery), prevention of stroke in non-valvular atrial fibrillation
- MoA: factor Xa inhibitor
- Not recommended in elevated LFT’s, may adjust dose for renal impairement
- Monitoring not required
6
Q
Dabigatran
A
- Indications: Acute treatment of VTE after at least 5 days of initial parenteral anticoagulation, long term anticoagulation for prevention of VTE, thromboprophylaxis for VTE (i.e. elective hip or knee replacement surgery), prevention of stroke in non-valvular atrial fibrillation
- MoA: direct thrombin inhibitor
- Not recommended in severe renal impairement and elevated liver enzymes
- Main side effect: dyspepsia
7
Q
Rivaroxaban
A
- Indications: Acute and long-term anticoagulation for VTE, thromboprophylaxis for VTE (i.e. elective hip or knee replacement surgery), prevention of stroke in non-valvular atrial fibrillation
- MoA: factor Xa inhibitor
- Administer with food to enhance bioavailability
- No renal dose adjustment for VTE indication
- Major bleeding risk same as warfarin- increased in elderly, prior haemostatic defects and renal impairement
8
Q
Von Willebrand disease (VWD)
A
- Inherited quantative or qualitive deficiency of von Willebrand factor (VWF)
- VWF is synthesised by endothelial cells and Megakarocytes
- Autosomal inheritance: females 2-3x more common
9
Q
Clinical features of Von Willebrand disease (VWD)
A
- Mucocutaneous bleeding: Heavy menstrual bleeding, Epistaxis, Bruising, Excessive bleeding from minor wounds, GI bleeding, Oral cavity/post-dental procedure, Post-operative, Post-partum
- Musculoskeletal bleeding (Type 3 VWD): Hemarthrosis, Soft tissue, muscle hematoma
10
Q
Type 1 VWD- 80%
A
- Mild-moderate quantitative deficiency of VWF and factor VIII. Functionally normal VWF
- Autosomal dominant/co-dominant trait with variable penetrance and expressivity
- Symptoms: mild mucocutaneous bleeding, Menorrhagia. Epistaxis and bruising in children.
- Severe symptoms if VWF levels <0.15 IU/ml
- Type 1C – clinically relevant, associated with heightened VWF clearance
11
Q
Type 2 VWD- 20% subtypes
A
Four major subtypes
1. 2A – abnormal assembly or reduced half-life of high molecular weight multimers (HMWM)- not the right size
2. 2B – increased binding of VWF to platelets causing depletion of HMWM and thrombocytopenia. VWF not the right size and too active
3. 2M – decreased binding of VWF to platelets but with normal VWF multimers distribution. FVIII still binds normally
4. 2N – markedly decreased binding of VWF to Factor VIII, causing low plasma factor VIII levels (autosomal recessive)
12
Q
Type 2 VWD
A
- Normal levels f VWF just functionally defective (for type 2A, 2B, 2M - VWF activity: antigen ratio to be discrepant, i.e. <0.60)
- Generally autosomal dominant trait
13
Q
Type 3 VWD (<1%)
A
- Quantitative absence of VWF (<1% of normal) and low FVIII levels (FVIII activity in the range of mild-moderate hemophilia A)
- Virtually complete deficiency of VWF
- Autosomal recessive
14
Q
Acquired von Willebrand syndrome (AVWS)
A
- Typically presents in people >40 years old and with no prior bleeding history. Mainly due to underlying condition:
- Lymphoproliferative disease
- Myeloproliferative disease
- Malignancy: due to aberrant binding of VWF to tumour cells
- Shear induced VWF conformational changes (e.g. aortic valve stenosis, ventricular septal defect)
- Autoimmune conditions
15
Q
VWD investigations
A
- Bleeding symptoms can be assessed with quantitative bleeding assessment tool (BAT) such as the International Society on Thrombosis and Haemostasis (ISTH)
- FBC, PT, APTT
- VWD screen: FVIII, VWF antigen, activity (ristocetin or non-ristocetin based, i.e. collagen)
- PFA-100 (“in vitro bleeding time”) and blood type
- If clinically indicated: If suspect Type 2, order RIPA (ristocetin-induced platelet agglutination) and multimer studies
- VWF genetic testing (speak to coagulation lab)
16
Q
Diagnosing VWD
A
- VWF antigens (Ag): diagnosis when VWF levels are <0.30 IU/ml in the context of a previous mucocutaneous bleeding history. If levels undetectable= Type 3
- VWF activity: Assessed by measuring ristocetin cofactor (RCo) and collagen binding (CB) as ratios of VWF antigen levels
- RCo/Ag and CB/Ag is >0.6= Type 1
- RCo/Ag or CB/Ag is <0.6= Type 2
17
Q
Management of VWD
A
- Type 1, Type 2A, Type 2N VWD patients who are known to be responsive to DDAVP (desmopressin)
- Desmopressin side effects: flushing, tachycardia and headache. Generally avoided if have cardiac risk factors or >65
18
Q
Other management of VWD
A
- For other VWD or inadequate response to desmopressin: Humate P or Wilate
- Antifibrinolytic agents especially for GI, gynecologic and nasopharyngeal bleeding: tranexamic acid. Contraindicated in hematuria
- Cryoprecipitate: use 8-12 bags q 12-24 hours as needed ONLY if Humate P/Wilate unavailable
- If hemorrhage not controlled despite adequate FVIII levels, platelet transfusion may be helpful
19
Q
Specific situations in VWD
A
- Pregnancy: Factor VIII levels are best predictor of bleeding during delivery. Should be given tranexamic acid to take at home post discharge
- Heavy menstrual bleeding: COCP, IUS, endometrial ablation
- Allo-antibodies to VWF: very rare, can occur in type 3 disease. Repeated exposure to concentrate containing VWF can cause anaphylaxis
20
Q
Symptoms of VWD
A
- Excessivebruising
- Prolonged bleeding post surgery
- Bleeding gums
- Menorrhagia
