Haemostasis + Bleeding Disorders Flashcards by Daniel Part

What are the results of hypoperfusion?

Systemic acidosis (pH <7.35)
Microcapillary thrombus:
- Patchy tissue injury
- Large vessel thrombus -> Organ infarction
Eventual cellular necrosis

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How might shock be recognised initially?

Mottling
GCS <15:
- Confusion
- Agitation
Urine output <0.5ml/kg/hr

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How is shock confirmed?

Lactate levels:

> 2mmol/L is arguably diagnostic
> 4mmol/L results in significant mortality

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What is cardiogenic shock?

Reduced force of contraction and reduced stroke volume
Results in:
- Reduced CO
- Reduced MAP

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How can compensation occur in cardiogenic shock?

Increased SVR:

- Cool, clammy peripheries

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What are some causes of cardiogenic shock?

Arrhythmia
Poisoning
MI
Cardiomyopathy
Valve failure

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What clinical signs might be seen in obstructive shock?

Increased JVP

Distended neck veins

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What are some causes of obstructive shock?

Cardiac tamponade
Tension pneumothorax
Pulmonary embolus

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How does hypovolaemic shock come about?

Reduced blood volume
Reduced venous return (reduced EDV)
Reduced force of contraction and CO

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What is Class I of blood volume loss?

<15% (<750ml)

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What is Class II of blood volume loss?

<30% (<1500ml)

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What is Class III of blood volume loss?

<40% (<2000ml)

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What is Class IV of blood volume loss?

> 40% (>2000ml)

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What is the pathogenesis of distributive shock?

Reduced SVR due to vasodilation:
- Warm, red peripheries
Reduced MAP
Compensatory increase in CO

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What can cause distributive shock?

Inflammation:
- Sepsis
- SIRS
- Anaphylaxis
Neurogenic:
- Spinal cord damage

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What are the three categories of aetiologies for causes of platelet plug formation failure?

Vascular abnormalities
Platelets:
- Thrombocytopaenia
- Reduced function
von Willebrand factor

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What hereditary vascular abnormalities can cause a failure of platelet plug formation?

Haemorrhagic telangiectasia (Osler-Weber-Rendu)
CTDs:
- Ehlers-Danlos
- Marfan's
- Osteogenesis imperfecta

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What acquired vascular abnormalities can cause a failure of platelet plug formation?

Vasculitis:
- HSP
- Rheumatic disorders
Severe infections (Meningococcus, Measles, Typhoid)
Drugs:
- Steroids
- Sulfonamides

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What acquired disorders result in reduced platelet formation (thrombocytopaenia)?

General bone marrow failure
MDS
Myeloma
Solid tumour infiltration
Aplastic anaemia

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What acquired disorders result in increased platelet destruction/sequestration?

Coagulopathy (DIC)
Autoimmune (ITP)
Hypersplenism
TTP

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What are some examples of acquired platelet function defects?

MPDs
Renal and liver disease
Paraproteinaemias
Drugs:
- Aspirin
- NSAIDs

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What is an acquired cause of vWF deficiency?

Thrombocythaemia:

- vWF sequestration

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What are some hereditary causes of vWF deficiency?

Autosomal dominant:

Most common factor deficiency
Usually mild (but variable)

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What causes failure of fibrin clot formation?

Multiple clotting factor deficiencies:
- Usually acquired (eg. DIC)
Single clotting factor deficiency:
- Usually hereditary (eg. Haemophilia)

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What can cause multiple factor deficiencies?

``` Liver failure Vit. K deficiency/Warfarin therapy Complex coagulopathy (DIC) ```

How do multiple factor deficiencies affect clotting assays?

Prolonged: - PT - APTT

Where are coagulation factors synthesised?

Hepatocytes

What factors are carboxylated by Vit. K?

II VII IX X

Where is Vit. K absorbed?

Upper intestine

What does Vit. K require for absorption?

Bile salts

What can cause a Vit. K deficiency?

``` Poor dietary intake Malabsorption Obstructive jaundice Warfarin Haemorrhagic Disease of the Newborn ```

What does clotting factor consumption in DIC cause?

Bruising Purpura Generalised bleeding

What can cause DIC?

Sepsis Obstetric emergencies Malignancy Hypovolaemic shock

How is haemophilia inherited?

X-linked

What is Haemophilia A?

Factor VIII deficiency

What is Haemophilia B?

Factor IX deficiency

What type of Haemophilia is more common?

A (by 5x)

What vessels bleed in Haemophilia?

Medium-large

What are the clinical features of Haemophilias?

``` Recurrent haemarthrosis Recurrent soft tissue bleeds (bruising in toddlers) Prolonged bleeding after: - Dental extractions - Surgery - Invasive procedures ```

How does haemophilia affect clotting assays?

Isolated prolonged APTT

What is an arterial thrombus rich in?

Platelets

How is an arterial thrombus treated?

Aspirin (and other anti-platelets) | Modify risk factors for atherosclerosis

What is a venous thrombus rich in?

Fibrin

How is a venous thrombus treated?

Heparin Warfarin New oral anticoagulants

What is the most common hereditary thrombophilia? What is its pathophysiology?

Factor V Leiden: | - Reduced activated protein C degradation of Factor V

What are some other causes of hereditary thrombophilia?

Prothrombin 20210 mutation Antithrombin deficiency Protein C or S deficiency

How does antiphospholipid syndrome affect clotting assays?

APTT prolonged

When an atherosclerotic plaque ruptures, what do platelets adhere to?

Released vWF | Exposed endothelial collagem

What do platelets release when activated?

ADP | Thromboxane A2

How do platelets aggregate?

Attach to each other via: - GbIIb/IIIa - Fibrinogen

Why do platelets alter shape on activation?

To expose more phospholipid

Via what receptors do platelets become activated?

ADP

How does aspirin work?

Inhibits cyclooxygenase: - Reduced Thromboxane A2 production - Reduced aggregation and activation

What are the side effects of aspirin?

Bleeding Blocks prostaglandin production: - GI ulcers - Bronchospasm

How do ADP receptor antagonists work?

Bind irreversibly to P2Y12 subtype

What are some examples of ADP receptor antagonists?

Clopidogrel | Prasugrel

How does Dipyridamole work?

Phosphodiesterase inhibitor: | - Reduces cAMP production

What type of drug is Abciximab? How does it work?

GPIIb/IIIA inhibitor: | - Inhibits aggregation

When should anti-platelets be stopped before elective surgery and why?

7 days They have a 7-10 day lifespan: - Drug affects them for their entire lifespan

How does heparin work?

Potentiates antithrombin (III): - Inhibits thrombin (IIa) - Inhibits Xa

How is heparin administered?

IV | S/C

Why do LMWHs only inhibit factor Xa?

To inhibit thrombin (IIa), heparin must bind to antithrombin (III) AND thrombin (IIa) LMWHs are too small: - Can only bind factor Xa - Cannot bind both III and IIa

How is unfractionated heparin monitored?

APTT

How are LMWHs monitored?

Anti-Xa assay

When may LMWH monitoring be used?

Renal failure

What is heparin induced thrombocytopaenia/with thrombosis?

>50% drop in platelets: | - Usually >=5 days of therapy

What long term complication can arise with heparin therapy?

Osteoporosis

How can heparin be reversed?

``` STOP IT (short half-life) Protamine sulphate IV: - Reverses AT III - Complete reversal for unfractionated heparin - Partial reversal for LMWH ```

When is phenindone used?

If resistant/intolerable of warfarin

Where is warfarin absorbed?

Upper intestine (requires bile salts)

Why is the carboxylation if factors II, VII, IX and X important?

Both -COOH groups are required for the factors binding, via calcium ions, to phospholipid Without both groups: - Bond too weak - Inefficient coagulation

When is initial dosing of warfarin slow?

AF Liver disease Malnourished Elderly

What is the first typical dose of warfarin?

10mg dose at 6pm on day 1

How is warfarin maintained?

INR daily for first 5 days: | Take warfarin at same time every day

What is the target INR?

2-3 3. 5 (3-4) in recurrent VTE 2. 5-3.5 if mechanical heart valves

How is INR calculated?

(Patient's PT in secs/Mean normal PT in secs)^ISI

How can warfarin be reversed?

``` Stop warfarin Administer oral Vitamin K Administer clotting factors: - FFP or - Factor concentrates ```

How does Dabigatran work?

Oral direct thrombin inhibitor

How can Dabigatran be reversed?

Idracizumab

What drugs are examples of oral direct Factor Xa inhibitors?

Rivaroxaban | Apixaban

When are newer oral anticoagulants used?

Prophylaxis in elective hip +/or knee replacements (instead of LMWH) Stroke prevention in AF for some Treatment of DVT/PE

What is primary haemostasis?

Formation of platelet plug

What is secondary haemostasis?

Formation of fibrin clot

What are the consequences of the failure of platelet plug formation?

``` Spontaneous bleeding and purpura Mucosal bleeding: - Epistaxis - GI - Conjunctival - Menorrhagia Intracranial haemorrhage Retinal haemorrhage ```

Haemostasis + Bleeding Disorders Flashcards

(84 cards)