Haemostasis, Thrombosis and Embolism

Question 1

What is the aim of haemostasis?

Answer 1

To prevent bleeding and unnecessary coagulation, allow blood to flow, make, control then breakdown a clot.

Question 2

After vascular injury, what is the haemostasis pathway?

Answer 2

Vascular injury, platelet-collagen adhesion, platelets attach to fibrinogen, immobilised fibrinogen attract factors of blood coagulation which transformers fibrinogen into fragments of fibrin. 24-48 hours later, molecules of plasminins are attracted to the fibrin net and destroy it, fibrinolytic breakdown products are phagocytosis by macrophages and eosinophils and normal blood flow is restored.

Question 3

The essentials of haemostasis:
Keep blood ________ (heart, venous valves, _____ pump, BVs are important), platelets, coagulation and anticoagulation _________.

Answer 3

Moving
Calf
Factors

Question 4

When _______ cleaves fibrinogen to fibrin, it strengthens the platelet _______ for a more ______ clot.
Clot initiation, formation and ______________.

Answer 4

Thrombin
Plug
Stable
Fibrinolysis

Question 5

How are platelets derived, what is the normal platelet count and what is their lifespan?

Answer 5

Megakaryocytes produce platelets in the bone marrow, as they bud off from the cytoplasm. Normally the count is 150-400x10(to the power of 9)/L and the normal lifespan is 7-10 days.

Question 6

Explain the process of platelet adhesion.

Answer 6

Damage to the vessel wall and exposure of underlying tissue (collagen). Platelets adhere to collagen via the VWF (Von Willebrand Factor) receptor.

Question 7

Explain the process of platelet activation.

Answer 7

Once adhered, platelets secrete ADP and thromboxane etc to activate the,selves and others. They are involved in the activation of the clotting cascade and provide some factors by secretion from internal stores.

Question 8

What is the cross linking of platelets to form a platelet plug known as (after adhesion and activation)?

Answer 8

Platelet aggregation.

Question 9

In platelet clotting, mediating factors can be sites for targeting for drugs, give some examples of mediating factors.

Answer 9

Platelet receptors - glycoproteins complexes, Von Willebrand Factor, fibrinogen, collagen, ADP, thrombin, thromboxane/arachidonic acid.

Question 10

Clotting cascade:
Amplification system activates ________ proteins –>thrombin (IIa), which converts soluble ___________ into insoluble _______, which enmeshes the initial _________ ______ to form a stable clot. It’s controlled by natural ______________ which inhibit activation and carefully balance the clot destroying proteins activated by the cascade.

Answer 10

Precursor
Fibrinogen
Fibrin
Platelet plug
Anticoagulants

Question 11

Factors involved in the clotting cascade are made in the liver, what is measured to assess the extrinsic and intrinsic pathways and which factors are used?

Answer 11

The extrinsic pathway is measured by PT and uses VII.
The intrinsic pathway is measured by APTT and uses factors VIII, IX, XI and XII (if lowered, APTT increases).
Both feed into the cascade to use V, X, prothrombin and fibrinogen.

Question 12

What is the Thrombin burst and how does it come about?

Answer 12

Initiation –> event –> tissue factor exposure activates FVII - prothrombin –> thrombin. Amplification as activated clotting factors increase the production of thrombin leading to the Thrombin burst - initial small amount of thrombin feedback.

Question 13

What does Von Willebrand Factor do?

Answer 13

Platelet adhesion to the vessel wall, platelet aggregation and carries FVIII.

Question 14

In the process of clotting, how is the vessel wall involved?

Answer 14

It vasoconstriction, produces vWF, exposes collagen and tissue factor, so initiates the activation of clotting factors.

Question 15

Natural anticoagulants stop further coagulation, name some, describe a consequence of their deficiency and explain the clinical relevancy.

Answer 15

Protein C, S, antithrombin. Thrombophilia if deficiency - excessive clotting. There’s clinical relevance with bleeding, arterial/venous thrombotic disorders, abnormal blood test results and drug therapy.

Question 16

Bleeding disorders can be acquired or inherited and the result of which 3 things/abnormalities?

Answer 16

Due to an abnormal vessel wall, platelets or coagulation factors.

Question 17

Give an example of an acquired and an inherited coagulation factor disorder.

Answer 17

Congenital - Haemophilia (A=FVIII and B=FIX).

Acquired - liver disease, vitamin K deficiency, anticoagulants e.g. Warfarin (inhibits vitamin K).

Question 18

The clinical severity of coagulation factor disorders correlates to the extent of the efficiency, give some examples of possible consequences.

Answer 18

Muscle haematomas, recurrent haemarthrosis, joint pain and deformity, prolonged bleeding post dental extraction and surgery and post trauma (life threatening) and intracerebral haemorrhage.

Question 19

Haemophilia A is ____________ recessive and may be mild/moderate/severe depending on the amount of _______. It is diagnosed ___________\____ ______ ______ and in infancy if __________ mutation. It’s treated with recombinant factor __. Haemophilia B has a similar presentation, but has a congenital ____________ in _____.

Answer 19

X-linked
FVIII
Prenatal/soon after birth
Spontaneous
VIII
Reduction 
IX

Question 20

Von Willebrand’s Disease is relatively common (usually inherited _________ ________). There is reduced platelet _________ to the vessel wall and abnormal _____ activity. It may be caused by several genetic defects. Usually associated with low a reduction of vWF production.

Answer 20

Autosomal dominant
Adhesion
FVIII

Question 21

Low platelet associated bleeding is a result of Von Willebrand’s Disease, what might occur?

Answer 21

Skin and mucous membrane bleeding (epistaxis (nose bleed), gum bleeding and bruises), or prolonged bleeding after trauma (heavy periods, post op/dental extraction). Unlike with Haemophilia, spontaneous joint or muscle bleeds are rare.

Question 22

What may result from vessel wall abnormalities/disorders?

Answer 22

Easy bruising, spontaneous bleeding from small vessels (mainly skin, can be mucous membranes).

Question 23

Give an example of a congenital vessel wall abnormality.

Answer 23

Hereditary Haemorrhagic Telangiectasia (HHT), an autosomal dominant Disease with dilated micro vasculature swellings with time and GI haemorrhages leading to Fe deficiency anaemia.
Or a connective tissue disorder such as Ehlers-Danlos.

Question 24

Give an example of an acquired vessel wall abnormality.

Answer 24

Senile purpura, steroids, infection, scurvy (defective collagen production).

Question 25

Platelet disorders include those that are qualitative disorders of platelet function and may be either acquired or inherited, give an example of each.

Answer 25

Hereditary (rare) - Bernard Sonlier, associated with impaired platelet granule content release.
Acquired (common) - aspirin/NSAIDs/dopidogrel (antiplatelet drugs), anaemia, myeloproliferative disorders and renal failure.

Question 26

Quantitative disorders with a low platelet count come from either reduced production or increased removal (differentiate with bone marrow biopsy). Describe some issues with increased removal (2 types).

Answer 26

Immune destruction e.g. Immune thrombocytopenic purpura, which can be secondary to autoimmune disease, treated with immunosuppression, as platelet transfusions don’t work.
Non-immune destruction e.g. Microangiopathic haemolytic states (including DIC) and cardiopulmonary bypass surgery or splenic pooling.

Question 27

Give some examples of reduced platelet count due to decreased production.

Answer 27

B12/folate deficiency, infiltrated bone marrow (cancer/fibrosis), drugs, viruses.

Question 28

What are the consequences of severe thrombocytopenia?

Answer 28

It’s generally asymptomatic until platelet count < 30, then easy bruising, petechiae (small red dots), purpura, mucosal bleeding, severe bleeding after trauma and rarely intracranial haemorrhage.

Question 29

What is DIC (disseminated intravascular coagulopathy) and how is it treated?

Answer 29

Microangiopathic haemolytic anaemia - pathological activation of coagulation resulting in numerous microthrombi, so clotting factors and platelets get used up, so clotting tests affected (if trauma, may bleed out). There must always be a trigger, so treat that: malignancy, massive tissue injury (burns), infections (gram negative sepsis), massive haemorrhage and transfusion, ABO transfusion reaction or obstetric causes.

Question 30

What is thrombosis?

Answer 30

The formation of a solid mass of blot within the circulatory system.

Question 31

What causes thrombosis to occur?

Answer 31

Occurs because of abnormalities in the vessel wall (atheroma, direct injury, inflammation), abnormalities of blood flow (stagnation, turbulence) or abnormalities in the blood components (smokers, post partum or operation).

Question 32

How do arterial thrombi appear?

Answer 32

Pale, granular, have lines of Zahn (layered appearance due to varying constituents of thrombus), lower cell content. RBC content accounts for the spectrum of pale to red.

Question 33

Describe the appearance of a venous thrombus.

Answer 33

Soft, gelatinous, deep red with a high cell content.

Question 34

What are the 5 possible outcomes of thrombosis?

Answer 34

Recanalisation,
Embolism,
Organisation,
Propagation,
Lysis.

Question 35

Lysis is the complete ___________ of a thrombus. With the ___________ system active, blood flow is ___________ (most likely when thrombi are ______).

Answer 35

Dissolution
Fibrinolytic
Reestablished
Small

Question 36

What is propagation of a thrombus?

Answer 36

The progressive spread of a thrombus, distally in arteries and proximally in veins (direction of blood flow) - repeated event with gradual enlargement.

Question 37

What is the natural history of most thrombi and how does it work?

Answer 37

Organisation is a reparative process, with the ingrowth of fibroblasts and capillaries, much like granulation tissue. The lumen remains obstructed, so flow is not restored.

Question 38

What outcome of a thrombus means that blood flow is reestablished, but usually incomplete, with one or more channels formed through an organising thrombus?

Answer 38

Recanalisation.

Question 39

What is meant when saying that a thrombus embolises?

Answer 39

Part of the thrombus breaks off, travels through the blood stream and lodges at a different site.

Question 40

What are the differing effects of arterial and venous thrombi?

Answer 40

Arterial thrombi can lead to ischaemia, infarction, depending on the site and collateral circulation, whereas a venous thrombus may cause congestion, oedema (increased hydrostatic pressure), ischaemia and infarction (if/when tissue pressure reaches arterial pressure so nothing can come in).

Question 41

Define embolism and describe some types.

Answer 41

The blockage of a blood vessel by a solid, liquid or a gas at a site distant from its origin.
90% of emboli are thrombo-emboli, but other types include amniotic fluid, nitrogen, medical equipment, fat or tumour cells.

Question 42

What are the different types of thrombo-emboli?

Answer 42

Some pass from the systemic veins to the lungs = pulmonary emboli, some from the heart pass through the aorta to the renal, mesenteric and other arteries, from atheromatous carotid arteries can pass to the brain and from an atheromatous abdominal aorta to the arteries of the leg.

Question 43

List some predisposing factors for DVT.

Answer 43

Immobility/bed rest, post-operative, pregnancy and post-partum, oral contraceptives, severe burns, cardiac failure, disseminated cancer (think Virchow’s triad).

Question 44

How can the risk of DVT (and so PE) be reduced?

Answer 44

With various hospital protocols e.g. Stockings with graduated pressure or ‘Flowtron’ boots, which intermittently inflate.

Question 45

How might DVT be treated?

Answer 45

With IV heparin type drugs or oral warfarin, which prevent propagation (are anticoagulants), but aren’t fibrinolytic.

Question 46

What’s the difference between massive, Major and minor pulmonary emboli?

Answer 46

A massive PE, >60% reduction in blood flow, is rapidly fatal. A major PE shows medium sized vessels blocked and patient’s short of breath (with or without a cough and blood stained sputum). A minor PE has small peripheral pulmonary arteries blocked and is asymptomatic or comes with minor shortness of breath.

Question 47

What is the issue with recurrent minor pulmonary emboli?

Answer 47

They can lead to pulmonary hypertension.

Question 48

What type of embolism is commonly, but not always associated with a bone fracture?

Answer 48

A fat embolism.