Assessing Haemostasis

Steps of Haemostasis

• Five key steps: vessel spasm, platelet plug formation, coagulation, clot retraction, fibrinolysis.

Initial Platelet Interaction

• vWF (von Willebrand factor) binds collagen exposed at damaged sites and the GPIb complex on platelet surfaces, slowing platelet movement.

Platelet Activation Process

• Platelet rolling occurs as GPVI receptor binds collagen, triggering a signaling cascade that increases intracellular calcium.
• Increased calcium leads to granule secretion, conversion of αIIbβ3 to a high-affinity state, and changes in platelet shape.

Fibrinogen Role in Platelet Plug Formation

• Converted fibrinogen receptor (αIIbβ3) on platelets binds fibrinogen, cross-linking platelets to form a stable plug.

Fibrinogen Receptor Abundance

• Approximately 80,000 copies of the fibrinogen receptor (αIIbβ3) exist on each platelet, facilitating effective platelet aggregation.

Analogy for Fibrinogen Connectivity

• A comparison to individuals linking hands across multiple Millennium Stadiums illustrates the extensive connectivity provided by abundant receptors.

Types of Platelet Receptors

• Platelets contain various receptors: Receptor Tyrosine Kinases (RTKs), G Protein-Coupled Receptors (GPCRs), and Integrins, each serving unique functions in activation and signaling.

Coagulation Process

• Coagulation transforms fluid blood into a gelatinous clot, stabilizing the platelet plug.
• Thrombin converts prothrombin to thrombin, then converts fibrinogen to fibrin.

Fibrinolysis

• Plasminogen is activated to plasmin, leading to the breakdown of fibrin and the resolution of clots.

Causes of Bleeding Disorders

• Result from deficiencies in platelet number/function or coagulation factors.

Causes of Thrombosis

• Arterial thrombosis arises from inappropriate platelet stimulation, such as ruptured atherosclerotic plaques.
• Venous thrombosis is often due to a lack of coagulation inhibitors.

Normal Haemostasis Steps

• Sequence includes collagen exposure, platelet adhesion, activation, secretion, aggregation, and ultimately, platelet plug formation.

Outcome of Normal Haemostasis

• Successful formation of a platelet plug at the injury site, crucial for preventing excessive bleeding.

Consequences of Arterial Thrombosis

• Can lead to myocardial infarction (MI), ischemic stroke, and peripheral artery disease (PAD).

Venous Thrombosis Consequence

• Primarily causes deep vein thrombosis (DVT) with clot formation in the veins, typically in the legs.

Thrombotic Pathology Mechanism

• Stable clot formation disrupts normal blood flow, can occur in arteries or veins, and involves coagulation activation.

Signs and Symptoms of Thrombotic Disorders

• Symptoms vary by location: chest pain for coronary arteries, FAST sequence for carotid arteries, unilateral leg pain for deep vein thrombosis.

Bruise (Haematoma) Characteristics

• Result from blood vessel tearing, showing color changes as blood is phagocytosed and degraded over time.

Colour Changes in Bruises

• Red-blue indicates haemoglobin, green signifies biliverdin, yellow indicates bilirubin, and golden represents hemosiderin.

Haematoma Definition

• Purple/red discoloration caused by bleeding under the skin.

Types of Haematomas

• Petechiae: small spots (1cm or less), larger hematomas represent pooling in the tissue.

Vascular Defects

• Abnormal bleeding can occur from weak vessels that leak.

Thrombocytopenia

• A deficiency of platelets that leads to abnormal bleeding.

Disorders of Platelet Function

• Abnormal bleeding stemming from dysfunction of platelet components.

Coagulation Issues

• Abnormal bleeding can arise from coagulation process deficiencies.

Clinical Features of Bleeding Disorders

• Common clinical features include bleeding, petechiae, and epistaxis for primary and coagulation disorders; menorrhagia and haemarthroses distinguish primary from coagulant disorders.

Investigation Process in Haemostatic Disorders

• Involves personal and family medical history, risk factor assessment, and blood tests.

Full Blood Count (FBC)

• Provides data on the number and types of blood cells present.

Bleeding Time

• Normal range: 3-8 minutes. Observes how long it takes for bleeding to stop after a small incision.

PFA-100

• Modern test evaluating platelet function and plug formation using citrated blood.

Platelet Aggregation Studies

• Measure light absorbance drop in platelet-rich plasma during aggregation using agents such as ADP and collagen.

Flow Cytometry

• Analyzes platelet surface proteins, increasingly used to identify defects.

Serum Thromboxane Levels

• Reflect thromboxane involved in platelet activation; reduced levels indicate aspirin's antiplatelet effect.

Aspirin Usage

• Commonly prescribed for reducing platelet activity to prevent arterial thrombosis.

Coagulation Assays

• Include Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT), used for monitoring bleeding disorders and anticoagulant therapy.

INR (International Normalized Ratio)

• Used to standardize PT results for warfarin therapy; normal ~1.0, therapeutic ranges vary based on condition treated.

Thrombin Time

• Evaluates how quickly fibrinogen converts to fibrin; normal range is 15-19 seconds.

Factor Assays

• Measure activity of specific coagulation factors; prolonged clotting time identifies deficiencies.

D-dimer Assays

• Elevations indicate the presence of thrombus; useful in diagnosing conditions like DVT.

PCR Testing

• Detects genetic abnormalities associated with bleeding disorders, allowing for pedigree, phenotype, and genotype analysis.

Test your knowledge on the coagulation process and haemostasis with this quiz. Explore essential components such as thrombin's function, the steps of normal haemostasis, and the role of plasmin in fibrinolysis. Challenge yourself to identify key characteristics of bruises and the types of receptors present on platelets.