Haemostasis and Clotting Flashcards
(55 cards)
1
Q
What is haemophilia C
A
- Jewish populations - Autosomal recessive
2
Q
What is deep vein thrombosis?
A
- when there is a clot in the deep vein of your legs,
3
Q
What are the compounds secreted by thrombocytes when they are activated, and what do each of them cause?
A
- ADP: activate platelets further
- Serotonin: vasoconstriction
- Thromboxane A2 (TxA2): vasoconstriction and aggregation
- Calcium and presence of phospholipids: allows coagulation reactions
4
Q
What are the compounds that initiate the internal and external coagulation cascades?
A
- Extrinsic (tissue factor) pathway: involves tissue factor
- Intrinsic (contact activation) pathway: thrombin, factor XIIa, a nucleation site, glass in a laboratory
5
Q
What are the enzymes directly responsible for transforming fibrinogen to a clot
A
- Prothrombin –> Thrombin: converts fibrinogen into fibrin
- Factor XIIIa, cross-links it into a clot
6
Q
What are the enzymes that are only part of the intrinsic (contact activation) coagulation pathway?
A
- factor XI
- factotor XII
- factor IXa
7
Q
What is the role of vitamin K in haemostasis?
A
- necessary for the production of Ca-dependent proteases in the liver - i.e factor II, VII, IX, X (extrinsic tissue factor pathway)
8
Q
What physiological state might lead a patient to develop a vitamin K deficiency?
A
- lack of bile salts, if exogenous lipids were not being properly digested
- Warfarin toxicity: prevents recycling of vitK
9
Q
What is the aetiology of haemophilia A
A
- a mutation in the factor VIII gene
- X-linked recessive disease
10
Q
What is the aetiology of haemophilia B?
A
- X-linked recessive - a mutation in the factor IX gene
11
Q
GIve an overview of how the body responds to an injury in a blood vessel
A
- formation of a haemostatic plug physically protects and coats the surface of the injury initially: platelet adhesion, activation and aggregation - coagulation - vasoconstriction: decreases local blood flow
12
Q
Explain the role of platelets in haemostasis?
A
- aggregate at the site of injury, over fibrinogen, forming a haemostatic plug - contribute to vasoconstriction by releasing vasoconstrictor compounds, serotonin TxA2 - secrete/provide compounds that encourage coagulation, including the phospholipids
13
Q
List 4 differentiated cell types that develop from the lymphoid precursor cells
A
- B cells - T helper cells - NK cells - Plasma cells
14
Q
List 4 differentiated cell types that develop from the myeloid precursor cells
A
- eosinophils - monocytes/macrophages - neutrophils - RBC
15
Q
Explain platelet activation
A
- change dramatically in response from ADP or exposed collagen
- more spindly shape
- metabolism goes up
- exocytose many granules
- their membranes gain proteins (GP2b/3a)
- many reactions of the clotting cascade can only take place on the membrane of an activated platelet
- platelet aggregation can only occur on the surface of already activated platelets
16
Q
What prevents blood from clotting spontaneously and inappropriately?
A
- Fibrinolysis.
- Anticoagulation factors.
- Maintaining platelets in the inactivated state.
- Keeping coagulation initiation signals sequestered (eg Factor III/Tissue factor behind the endothelium).
- Rapid blood flow
17
Q
What is Factor X and Xa?
A
- Factor Xa is an activated enzyme. It catalyses the conversion of prothrombin (factor II) to thrombin. Its activity is substantially increased when it combines with active factor five.
- Factor X is the inactive form of Factor Xa
18
Q
What is Xase?
A
- converts Factor X to Xa
- Intrinsic Xase is Factor IX + factor VIII,
- Extrinsic Xase is Factor VII + tissue factor
19
Q
What are the causes of bleeding?
A
- Vascular disorders
- Platelet disorders: thrombocytopenia, defective function
- defective coagulation: inherited v acquired
20
Q
where does the blood go
What are the different patterns of bleeding?
A
Vascular and platelet bleed cause:
- bleeding into mucous membranes and skin
Coagulation disorders cause:
- bleeding into joints and soft tissue
21
Q
Give examples of Inherited and acquired vascular bleeding
A
Inherited:
- Hereditary haemorrhagic telangiectasia (Oslo-Weber-Render syndrome), abnormal blood vessel formation, autosomal dominant
- Ehlers-Danlos syndrome: affects connective tissue
Acquired:
- Scurvy
- Steriods: corticosteroids in GI bleeding
- Senile
22
Q
What is the normal platelet count range?
A
- 150-400 x 109/L
- below 150 is thrmobocytopenia
- symptoms are seen when plts are <10
23
Q
What are some symptoms of thrombocytopenia?
A
- Aipistaxis
- GI bleeds
- menorrhagia
- bruising
24
Q
What are some causes of thrombocytopenia?
A
failure to produce
- selective megakaryocyte depression: drug toxixity or viral infection
- General bone marrow failure
Increased consumption
- immune and autoimmune
- idiopathic
- assoiciated ith systemic lupus erythematosus, CLL or lymphoma
- infections: Helicobacter pylori, HIV, malaria drug induced = heparin
25
What is ITP and what is its treatment?
Immune thrombocytopenia
- treat with corticosteroids
- intravenous immunoglobulins: rapid rise in platelet count
- sometimes a splenectomy
26
Explain Haemophilia A an B
_Haemophilia A_
- sex linked chromosome
- defect is in the absence of or low factor VII
- largely caused by missense or frameshift mutaions or deletion in the factor VII gene
_Haemophilia B_
- Christmas disease, incidence is 1/5 of Haem. A
- Factor IX deficiency
27
# Haeme. A and B are the same
What are the clinical features of haemophilia
- spontaneous bleeding into joints (haemarthrosis) and muscle
- unexpected post-operative bleeding
- chronic debilitating joint diseases
- family history in the majority of cases
28
Clinical diagnosis of haemophilia
_Prolonged Activated Partial Thromboplastin Yome (APTT)_
- Factor VII, IX, XI, XII assay in the intrinsic pathway
_Normal Prothrombin Time (PT)_
- testing factor II, V, VII, X in the intrinsic pathway
- Low factor VII or IX levels: the lower the % the more severe
29
What treatment is given for haemophilia?
- Infusions of recombnant VIII or factor IX to 50-100% normal
- if patients factor VIII is raised to 30-50% spontaneous bleeding should be controlled
- 1-Diamino-8-D-arginine vasopressin (DDAVP); alternative for increasing plasma factor VIII level in milder hameophiliacs
30
# also what is VWF?
What is Von Willebrand disease?
- reduced level or abnormal function of von Willebrand factor (VWF)
- caused by a variety of missense mutations. autosomal dominant disease
_VWF_
- produced in endothelial cells and megakaryocytes
- large multimeric protein that carries factor VIII in the blood, prevents its premature destruction
- promotes platelet adhesion
31
What is the presentation of von Willebrand disease?
- women are more badly to be affected than men at a given VWF level
- mucous membrane bleeding: epistaxes, menhorrhagia
- excessive blood loss from superficial cuts and abrasions
- operative ad post-truamatic haemorrhage
32
What are the lab tests for vWD?
- prolonged APTT
- normal PT
- low vWF level/ function
- low factor VIII level
- prolonged bleeding time
- defective platlet function
33
What is the treatment for vWD?
- antifibrinolytic agent: tranexamic acid for mild bleeding
- DDAVP infusion for type 1 vWD: releases VWF from endothelial cells 30 minutes after infusion
- high-purity VWF for patients with very low VWF levels
34
What are Acquired disorders of coagulation?
- Vitamin K deficiency
- Liver disease
- Disseminated intravascular coagulation
35
How does Liver disease affect coagulation?
- Biliary obstruction → impaired absorbiton of vitamin K. therefore decreased synthesis of clotting proteins
- Decreased thrombopoeitin production from the liver contributes to thrombocytopenia
- Impaired platlet function and fibrinolysis
36
Explain Disseminated Intravscular Coagulation
This is the widespread intravascular deposition of fibrin with consumption of coagulation factors and platlets
- occurs as a consquence of many disorders that release procoagulent material into the circulation or cause widespread endothelial damage or platelet agggregation
- causes both bleeding and thrombosis to occur
37
# Disseminated intravascular Disease
What is the lab presentation of meningococcal DIC
- Prolonged PT, APTT, TT
- Low fibrinogen
- low platelts
- Raised D-dimers or FDPs
38
What anticoagulent drugs are there?
- Heparin: used to treat- MIs, PE, DVTs
- Warfarin: used to treat- PEs, DVTs, AF, prothetic valves
Direct (novel) Oral anti-coagulants
- Direct thrombin inhibitors: dabigatran, argatroban
- Factor xa inhibitars: rivaroxaban, apixaban
39
Explain Vitamin K deficency and its role in coagulation disorders
- required for gamma-carboxylation of factors II, VII, IX, X
- Inhibited by warfarin: interferes with the action of vitamin K epoxide reductase leading to functional vitamin K deficiency
Deficiency can be due to:
- Malabsorption of vitamin K, or inadequete in the diet, or inhibited by drugs like warfarin
- Biliary obstruction (jaundice)
- Haemorrhagic disease of the newborn ( give 1mg at birth )
40
What are characterised as deep veins?
- Iliac Vein
- Femoral Vein
- Popilteal vein
- Tibial Vein
41
What would make a DVT more likely?
- more risk if a lot is above the knee as there is more risk of embolism
- occur in the deep veins where blood flow is slower
42
# Virchows Triad
What are risk factors for a DVT?
- Hypercoagulable state: pregnancy, contraceptive pills,
- Circulatory stasis: long periods of sitting/ inactivity
- Epithelial injury: IV drug abuse, cancer, post operative
43
What are the clinical presentations for DVTs, and possible differential diagnosis?
- asymptomatic
- unilateral calf swelling/heat/pain/redness/hardness
_Differential_
- cellulitis
- Baker's cyst
- muscular pain
Risk factors should be considered
44
How is a DVT diagnosed?
- a doppler ultrasound
- shows a lack of blood flow in the leg
- use a Wells score
- use of a D-dimer test: indicates activation of the clotting cascade
raised score indicates a DVT has a high predictive negative value
45
What is the initial treatment of a DVT?
- Therapeutic anti-coagulation using sub-cut LMW heparin: tinzaparin or enoxaparin
- Dosing is according to the patient's weight, no monitoring required
- if the patient has a renal impairment (creatinine clearances less than 30ml/min) anticoagulant with i.v. unfractionated heparin is used instead. This require monitoring
46
What is the subsequent treatment for a patient with DVT?
- oral warfarin for 3-5 days
- stop LMW heparin when INR (International Normalised Ratio, based on the prothrombin time) \> 2.0 for 2 days
- if it's there 1st DVT (femoral or iliac)- 6 months course of warfarin
- if it's there 2nd DVT/PE: lifelong warfarin
- INR should be maintained between 2.0-3.0
47
What are the classical symptoms of a Pulmonary embolism?
- Pleuritic pain
- acute dyspnoea
- haemoptysis (coughing up of blood)
- could cause syncope or death
On examination
- tachycardic
- tachypnoiec
- hypotensive
48
# saddle embolism, pre and post embolysis
What investigations can be done to confirm a Pulmonary embolism?
CTPA scan
- CT Pulmonary angiogram
49
What is and what can be seen in a V/Q scan when investigating a PE?
a V/Q scan, uses a radioisotope to get images of the lung
- under perfusion, even though ventilation is very good: V/Q mismatch
- underlying lung disease
intermediate scans (rarely done)
50
What can be seen on an ECG investigating a PE?
- Sinus tachycardia: an increase in pulse rate
- Atrial Fibrillation
- Right Heart strain: right bundle branch block, struggle to get blood through the right lung
- Classic: SI, QII, TIII pattern on the ECG (rare)
51
What does a CXR when investigating a PE show?
- usually normal
- may see a small effusion
- possibly linear atelectasis (shadowing)
52
What are the outcomes for a PE?
- 5% mortality with treatment: even with treatment
- 4% develop pulmonary hypertension: clots in the pulmonary circulation
- Cause of death in 10-30% of in-patient post mortems
- Up to 60% have micro-emboli at post mortem
- A leading cause of ‘preventable’ death in the western world (25,000 deaths/yr in England)
53
What is the signs and treatment for a massive PE?
- signs of shock, hypotension and acute SOB
- Mx: thrombolysis and iv heparin
- this presents with a 2-6% serious risk of bleeding
54
What is the standard treatment for a PE?
- LMW heparin injections – e.g. Tinzaparin
- Warfarin (target INR 2.5) for 6 months
- Consider underlying causes: possibly stop taking the pill
- LMW heparin is better if underlying cancer
- Inferior Vena Cava filters
- Consider a DOAC (NOAC) as an alternative
- Dabigatran p.o (direct thrombin inhibitor)
- Rivaroxaban p.o (direct Xa inhibitor)
55
What is a thrombophilia screen?
- occasionally in younger patients with VTE (Venous thromboembolism)
- Inherited risk factors
- factor V Leiden
- Prothrombin gene variant
_- Anti-thrombin deficiency, rare_
_- Protein C deficiency, rare_
_- Protein S deficiency, rare_
_natural anticoagulant, more prone to clotting if you are deficient in these_
- Acquired risk: anti-phospholipid syndrome
- increased risk of miscarriage
- the phospholipid is required as part of the formation of prothrombinase
