Case 6 - Clotting Disorders Flashcards
What are the disorders of the primary haemostasis?
- Abnormal platelet count
- Abnormal platelet time
What are the disorders of the secondary haemostasis?
- Intrinsic pathway: haemophilia A or haemophilia B
- Extrinsic pathway: factor VII deficiency
- Both pathways (Deficiency or inhibition of vitamin K-dependent coagulation factors II, VII, IX, and X AND Vitamin K antagonist therapy)
- What is the prothrommbin time?
- Which pathway is it used in?
- What can prolong it?
- Time it takes for the extrinsic system to produce fibrin polymers
- Extrinsic + common
- Warfarin, Factor II, V, VII and X deficiency (due to vit K def)
- What is INR?
- Which pathway is it used in?
- What is its clinical relevance?
- Comparing the lab specific prothrombin time to a standardized prothrombin time
- Normal: 1 .0
- Extrinsic + common
- Vitamin K deficiency or warfarin therapy monitoring
- What is the activated partial thromboplastin time (aPTT)?
- Which pathway is it used in?
- What can prolong it?
- Time it takes for the intrinsic system to produce fibrin polymers
- Intrinsic + common
- Heparin, Factor VIII, IX, XI, XII (but no bleeding diathesis) and
Von Willebrand’s Disease
- What is the thrombin time (TT)?
- Which pathway is it used in?
- What is its clinical relevance?
- Time it takes for fibrin polymers to form after adding thrombin
- Common
- Detect fibrinogen deficiency
What can be the reasons why PT and APTT are prolonged?
- Vitamin K deficiency: Liver disease, malabsorption
- DIC
- Rarely: Factor V or Factor X deficiency
What is disseminated intravascular coagulation?
Condition where procoagulant pathways are abnormally active resulting in formation of blood clots in small blood vessels throughout the body. Often associated with trauma, shock, and sepsis.
What are vitamin K dependant factors?
- Factor II
- Factor VII
- Factor IX
- Factor X
- Protein C
- Protein S
- What is 50:50 mixture test?
- When it is done?
- What do the results mean?
- When patient has abnormal PT or APTT, can test with mixed 50:50 patient’s blood and normal plasma
- If corrected, there is a deficiency of a Factor
- If uncorrected, there is an inhibitor of the coagulation factor.
What is VWD?
- Due to either a quantitative or qualitative abnormality of von Willebrand factor (VWF).
- It provides the critical link between platelets and exposed vascular sub endothelium
What inheritance pattern does VDW carry?
Autosomal dominant
What is type 1 VWD?
- Quantitative deficiency of VWF
- Mild disease, with some bruising/mucosal bleeding, menorrhagia and caution during dental extractions/surgery
What is type 2 VWD?
- Qualitative deficiency: usually underactive apart from rare type 2b in which it is overactive.
- Similar to Type 1 clinically.
- Avoid desmopressin because it will release VWF from stores, use VWF concentrate instead.
What is type 3 VWD?
- Little or no VWF
- Autosomal recessive trait
- Severe illness, with severe mucosal and joint bleeding.
- Extreme caution in surgery
What are the symptoms of VWD?
- Bleeding from minor wounds
- Post-operative bleeding
- Easy and excessive bruising (ecchymosis) – large bruises or bruising on the trunk or other areas
- Menorrhagia
- Epistaxis, GI bleeding
- Bleeding gums with brushing
- Petechiae: result of bleeding under the skin (small non raised patches)
What are the investigations for VWD?
- Normal PT
- APTT – Prolonged only if factor VIII is decreased sufficiently (less than 35% of normal). Often normal in T1 + 2.
- Decreased factor VIII levels: binds to vWF in blood to
- Von Willebrand factor antigen
How can Von Willebrand factor antigen be used to differentiate between type 1 and 2?
- If vWF activity: vWF antigen >0.6, then it is Type 1
- If vWF activity: vWF antigen <0.6, then it is Type 2
What is the treatment for VWD?
- Desmopressin can be used to stimulates the release of VWF (not used in type 3)
- VWF infusion
- Factor VIII infusion
- Antifibrinolytic drugs (aminocaproic acid and tranexamic acid): slows down break down of clots
What can be given to women with menorrhagia in VWD?
- OCP
- Antifibrinolytic drugs (aminocaproic acid and tranexamic acid): slows down break down of clots
What is haemophilia?
Bleeding disorder which results from the deficiency of a coagulation factor.
What is haemophilia A?
Deficiency of clotting factor VIII (80% of cases)
What is haemophilia B?
Deficiency of clotting factor IX (20% of cases)
What is the inheritance pattern for haemophilia?
- X-linked recessive
- Only men affected, females carriers
What are the symptoms of haemophilia?
- Bleed excessively in response to minor trauma
- Risk of spontaneous haemorrhage without any trauma
- Excessive bleeding after surgery, dental procedure
- Mucocutaneous bleeding: Easy bruising, GI bleeding, haematuria, epistaxis
- Musculoskeletal bleeding: pain and swelling (commonly extremities)
- Hemarthrosis: swelling of the joints (commonly knees, elbow and ankle) with pain
What are the investigations of haemophilia?
- Genetic testing
- PT and platelet count: normal
- APTT raised
- If APTT is raised, then do 50:50 mixture
What is the treatment for haemophilia A?
- Recombinant FVIII: Half-life of 8 hours, give OD-TDS.
- Desmopressin: Releases stored FVIII from vWF (SC, IV)
- Tranexamic acid: allows any clot to stay there for longer.
What is the treatment for haemophilia B?
- Recombinant FIX: Half-life is 18-24hrs, give OD.
- Tranexamic acid: allows any clot to stay there for longer.
What is VTE?
Venous thromboembolism (VTE) consists deep vein thrombosis (DVT) and pulmonary embolism (PE).
What is given as VTE prophylaxis?
- Anti-embolism stockings (AES)
- LMWH (enoxaparinux)
- Don’t giver warfarin
What are the risk factors for VTE?
- Immobility
- Recent surgery: anaesthesia can lead to immobility
- Long haul flights
- Pregnancy
- Hormone therapy with oestrogen (combined OCP and HRT for postmenopausal women)
- Malignancy
- Polycythaemia
- Systemic lupus erythematosus
How to manage VTE?
Once suspected, start LMWH and warfarin because warfarin takes 48 to 72 hours to reach its therapeutic range after which heparin can be stopped.
How can warfarin be reversed?
- IV Vitamin K with IV administration of a prothrombin complex concentrate (PCC), which contains the vitamin K-dependent clotting factors.
What is Virchow’s triad?
1) Endothelial injury to vessel wall
2) Abnormal blood flow (stasis)
3) Hyper coagulability of the blood
What is a major side effect of desmopressin?
- Can cause drop in BP
- Need to check if it suits the person
What is DVT?
Formation of a thrombus in the deep veins, usually of the leg, and when part of the thrombus breaks off, travels in the venous system to the heart and can cause PE if lodges in lungs.
What are the symptoms of DVT?
Normally unilateral:
- Calf or leg swelling
- Dilated superficial veins
- Progressive tenderness, dull pain to the calf
- Oedema
- Swelling, feeling of tightness or heaviness
- Colour changes to the leg
What will leg examination for DVT show?
- To examine for leg swelling measure the circumference of the calf 10cm below the tibial tuberosity.
- More than 3cm difference between calves is significant.
What are the investigations for DVT?
- Wells score >2, do D-dimer test
- D-dimer: 95% sensitive, useful for ruling out DVT
- If D-dimer>, then do compression ultrasound for confirmed diagnosis.
- Ultrasound will show obstructed veins, abnormal blood flow
How to treat DVT and PE?
- Acute: LMWH for 5 days
- Secondary: warfarin and DOAC/NOAC/factor Xa inhibitor
- IVC filter
- Thrombolysis : streptokinase
What is the INR range for warfarin in DVT and PE?
2.0-3.0
How long is warfarin given for in DVT and PE?
- First thrombosis: usually 3–6 months
- For confirmed thrombophilia and recurrent thrombosis: indefinite
What should be avoided with warfarin?
Clarithromycin and this will boost warfarin levels and prevent clotting from taking place
What is PE?
Obstruction of one or more pulmonary arteries by an embolism which can arise from DVT and embolise to the lungs via the IVC.
What are the effect of PE on heart?
- Sources of thrombi can break off and travel to heart
- Can lead to Cor pulomnale
- Can pass through left side of heart to brain and lead to a clot
What is a massive PE?
- Large clot which lodges in the right side of the heart, or in both pulmonary arteries (saddle embolus) or 1 of the pulmonary arteries
How does a massive PE present?
Syncope (loss of consciousness) as well as the other symptoms of PE
How is a massive PE defined?
Massive PE by the presence of arterial hypotension (systolic blood pressure less than 100 mmHg) or cardiogenic shock / cardiac arrest.
What are the symptoms of PE?
- Acute onset of symptoms: triggered by a specific event (on rising in the morning)
- Dyspnoea
- Tachypnoea (most common)
- Sudden chest pain – worse with inspiration
- Cough with/without haemoptysis
- Tachycardia, hypotension
- Signs of DVT
- Hypoxaemia
What investigations are done in PE?
ECG:
- Sinus tachycardia (most common)
- Right ventricular strain: inverted T wave.
- S1 Q3 T3: Look at leads V1 + V3. In lead 1 a deep S wave, lead 3 a deep Q wave and lead 3 an inverted T wave,
- ABG – Respiratory alkalosis. To compensate the lack of oxygen, patients usually hyperventilate.
What is the treatment algorithm after doing Wells Score?
- Wells score <4, D-dimer -ve, don’t have VTE
- Wells score <4, D-dimer +ve, do CTPA or V/Q.
- Wells score >4 do urgent CTPA or V/Q.
Which PE imaging cannot be done in pregnant women?
CTPA
What are the differentials for DVT?
- Cellulitis
- Baker’s cyst
- Superficial thrombophlebitis
Which bacteria are the cause of cellulitis?
- Staphylococcus aureus
- Streptococcus pyogenes
What is the treatment for cellulitis?
- Flucloxacillin
- Benzylpenicillin
What are the symptoms for cellulitis?
Red, swollen, painful, hot, often unilateral leg, fever, malaise, rigors
How is cellulitis diagnosed?
Clinically, blood cultures, wound swabs
- What factors does anti-thrombin work on?
- What else does anti-thrombin activate for inhibition of coagulation cascade?
Factor II (thrombin)
Factor IX
Factor X
- activates tissue plasminogen activator (tPA). tPA activates plasminogen to plasmin. Plasmin degrades fibrin
What is superficial thrombophlebitis?
- Inflammation and thrombosis of a superficial vein, most commonly in the leg.
- It may co-exist with DVT, and it rarely causes PE.
What are the clinical features of superficial thrombophlebitis?
Pain, tenderness, induration, and erythema overlying a superficial vein, often with a palpable cord (the thrombosed vein)
What is used to diagnose superficial thrombophlebitis?
- Typically, a clinical diagnosis
- Duplex ultrasound: thickened, non-compressible vein
What is the treatment for symptomatic superficial thrombophlebitis?
- NSAIDs (naproxen), compression, elevation of the affected limb
What is the treatment for superficial thrombophlebitis affecting more than 5cm of the vin?
Anticoagulation (LMWH)