Week 2 part 2

Question 1

Disseminated intravascular coagulation

Answer 1

Simultaneous coagulation and haemorrhage caused by the initial formation of thrombi which consume clotting factors (factors 5,8) and platelets, ultimately leading to bleeding.

Disseminated intravascular coagulation (DIC) is a rare but serious condition that causes abnormal blood clotting throughout the body’s blood vessels. It is caused by another disease or condition, such as an infection or injury, that makes the body’s normal blood clotting process become overactive

Question 2

Disseminated intravascular coagulation causes

Answer 2

Infection
Malignancy
Trauma e.g. major surgery, burns, shock, dissecting aortic aneurysm
Liver disease
Obstetric complications

Question 3

Management of Disseminated intravascular coagulation

Answer 3

Clinically bleeding is usually a dominant feature, bruising, ischaemia and organ failure
Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products
Treat the underlying cause and supportive management

Question 4

Disseminated intravascular coagulation features

Answer 4

Clinically bleeding is usually a dominant feature, bruising, ischaemia and organ failure

Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products

Question 5

Blood tests in Disseminated intravascular coagulation

Answer 5

Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products

Question 6

Immune thrombocytopenic purpura (ITP)

Answer 6

Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.

Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contract, adults tend to have a more chronic condition.

Question 7

Features of Immune thrombocytopenic purpura (ITP)

Answer 7

may be detected incidentally following routine bloods
symptomatic patients may present with
petichae, purpura, bleeding (e.g. epistaxis)

catastrophic bleeding (e.g. intracranial) is not a common presentation

Question 8

Immune thrombocytopenic purpura (ITP) management

Answer 8

first-line treatment for ITP is oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used - it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required

Question 9

Evan’s syndrome

Answer 9

ITP in association with autoimmune haemolytic anaemia (AIHA)

Question 10

Acquired causes of Platelet Functional Defects

Answer 10

Drugs (eg Aspirin, non-steroidal anti inflammatory drugs)

Renal failure

Question 11

Von Willebrand’s disease

Answer 11

Von Willebrand’s disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common.

Question 12

Causes of acquired Thrombocytopenia

Answer 12

Marrow failure

Peripheral destruction

Question 13

Commonest cause of primary haemostatic failure

Answer 13

Thrombocytopenia

Question 14

von Willebrand factor

Answer 14

large glycoprotein which forms massive multimers up to 1,000,000 Da in size
promotes platelet adhesion to damaged endothelium
carrier molecule for factor VIII

Question 15

Investigations for Von Willebrand’s disease

Answer 15

prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin

Question 16

Von Willebrand’s disease management

Answer 16

• tranexamic acid for mild bleeding
• desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
• factor VIII concentrate

Question 17

Type 3 von Willebrand’s disease

Answer 17

(most severe form) is inherited as an autosomal recessive trait. Around 80% of patients have type 1 disease

total lack of vWF (autosomal recessive)

Question 18

Type 1 Von Willebrand’s disease

Answer 18

type 1: partial reduction in vWF (80% of patients)

Question 19

Type 2 Von Willebrand’s disease

Answer 19

abnormal form of vWF present

Question 20

Hemophilia

Answer 20

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX (single factor deficiency)

Question 21

Features of hemophilia

Answer 21

haemoarthroses
haematomas
prolonged bleeding after surgery or trauma

Question 22

Investigations in hemophilia

Answer 22

prolonged APTT

bleeding time, thrombin time, prothrombin time normal

Question 23

Multiple clotting factor deficiencies

examples

Answer 23

Disseminated Intravascular Coagulation
Liver failure
Vitamin K Deficiency/Warfarin therapy

Question 24

Where are coagulation factors produced?

Answer 24

All coagulation factors are synthesised in hepatocytes

Reduced in liver failure

Question 25

What coagulation factors require carboxylation by Vitamin K for their function?

Answer 25

Factors II, VII, IX & X are carboxylated by vitamin K which is essential for function

Question 26

Sources of Vitamin K

Answer 26

Diet Intestinal synthesis Absorbed upper intestine Requires bile salts for absorption

Question 27

Causes of Vitamin K Deficiency

Answer 27

``` Poor dietary intake Malabsorption Obstructive jaundice Vitamin K antagonists (warfarin) Haemorrhagic disease of the newborn ```

Question 28

Haemophilia A

Answer 28

Haemophilia A (factor VIII deficiency)

Question 29

Haemophilia B

Answer 29

Haemophilia B (factor IX deficiency)

Question 30

Single Factor Deficiency examples

Answer 30

Haemophilia A and B | Isolated prolonged APTT

Question 31

Thrombotic Events

Answer 31

Arterial = Coronary, cerebral, peripheral Venous = Deep venous thromboses, Pulmonary Embolism

Question 32

Arterial thrombosis

Answer 32

Arterial thrombosis is a blood clot in an artery, which can be very serious because it can stop blood reaching important organs. Arteries are blood vessels that carry blood from the heart to the rest of the body and the heart muscle. Arterial thrombosis may be caused by a hardening of the arteries, called arteriosclerosis. This happens when fatty or calcium deposits cause artery walls to thicken. This can lead to a buildup of fatty material (called plaque) in the artery walls. This plaque can suddenly burst (rupture), followed by a blood clot.

Question 33

Management of Arterial thrombosis

Answer 33

Blood-thinning medicines (anticoagulants) Catheters Stents Medicines to interfere with or dissolve blood clots

Question 34

Venous thromboembolism: risk factors

Answer 34

``` increased risk with advancing age obesity family history of VTE pregnancy (especially puerperium) immobility hospitalisation anaesthesia central venous catheter: femoral >> subclavian ```

Question 35

What medications increase the risk of Venous thromboembolism?

Answer 35

combined oral contraceptive pill raloxifene and tamoxifen antipsychotics (especially olanzapine)

Question 36

Venous thrombosis

Answer 36

Venous thrombosis is when the blood clot blocks a vein. Veins carry blood from the body back into the heart. - Low pressure system. - Platelets not activated. - Activates coagulation cascade - rich in fibrin clot.

Question 37

Virchow’s triad

Answer 37

Stasis Vessel wall damage Hypercoagulability

Question 38

Venous thrombosis management

Answer 38

Heparin/warfarin/New oral anticoagulants (e.g. rivaroxiban)

Question 39

Deep Vein Thrombosis features

Answer 39

Pain in one leg (usually the calf or inner thigh) Swelling in the leg or arm Chest pain Numbness or weakness on one side of the body Sudden change in your mental state

Question 40

Potential features of pulmonary embolism include:

Answer 40

``` chest pain - typically pleuritic dyspnoea haemoptysis tachycardia tachypnoea respiratory examination - classically the chest will be clear ```

Question 41

Management of PE

Answer 41

apixaban or rivaroxaban (both DOACs) should be offered first-line following the diagnosis of a PE if renal impairment is severe (e.g. < 15/min) then LMWH, unfractionated heparin or LMWH followed by a VKA if the patient has antiphospholipid syndrome (specifically 'triple positive' in the guidance) then LMWH followed by a VKA should be used

Question 42

Hypercoagulability CAUSES

Answer 42

Associated with release of tissue factor, raised VWF and factor VIII

Question 43

Causes of inherited thrombophilia

Answer 43

factor V Leiden (activated protein C resistance): most common cause of thrombophilia prothrombin gene mutation: second most common cause Deficiencies of naturally occurring anticoagulants - antithrombin III deficiency - protein C deficiency - protein S deficiency

Question 44

Hereditary Thrombophilias

Answer 44

A group of genetic defects in which affected individuals have an increased tendancy to develop premature, unusual and recurrent thromboses.

Question 45

Consider Hereditary Thrombophilia Screening

Answer 45

``` Venous thrombosis <45 years old Recurrent venous thrombosis Unusual venous thrombosis Family history of venous thrombosis Family history of thrombophilia ```

Question 46

Causes of acquired Thrombophilia

Answer 46

Antiphospholipid syndrome Drugs - the combined oral contraceptive pill

Question 47

Management of Hereditary Thrombophilia

Answer 47

Advice on avoiding risk Short term prophylaxis to prevent thrombotic events during periods of known risk Short term anticoagulation to treat thrombotic events Long term anticoagulation ONLY if recurrent thrombotic events

Question 48

Risk factors for Recurrent Thrombosis

Answer 48

History of previous thrombosis Spontaneous thrombosis rather than acquired transient risk factor (eg immobility or surgery) Family history

Question 49

Antiphospholipid syndrome

Answer 49

``` Is an acquired thrombophilia Multi organ disease Arterial and venous thromboses Recurrent fetal loss Mild thrombocytopenia ```

Question 50

Investigations of Antiphospholipid syndrome

Answer 50

Either Lupus anticoagulant or Anti cardiolipin antibodies APTT usually prolonged Antibodies may be elevated following surgery, drugs or malignancy

Question 51

Management of Antiphospholipid syndrome

Answer 51

Need anticoagulation with INR between 3 and 4 (warfarin and aspirin)

Question 52

Conditions associated with Antiphospholipid Antibodies

Answer 52

Autoimmune Disorders Lymphoproliferative Disorders Viral Infections Drugs

Question 53

Complications of thrombosis

Answer 53

Thrombosis can block the blood flow in both veins and arteries. Complications depend on where the thrombosis is located. The most serious problems include stroke, heart attack, and serious breathing problems.

Question 54

Risk factors for arterial thrombosis may include:

Answer 54

``` Smoking Diabetes High blood pressure High cholesterol Lack of activity and obesity Poor diet Family history of arterial thrombosis Lack of movement, such as after surgery or on a long trip Older age ```

Question 55

Venous thrombosismay be caused by:

Answer 55

``` Disease or injury to the leg veins Immobility A broken bone (fracture) Certain medicines Obesity Autoimmune disorders that make it more likely your blood will clot ```

Question 56

D-dimer

Answer 56

D-dimer is a protein fragment (small piece) that's made when a blood clot dissolves in your body. Blood clotting is an important process that prevents you from losing too much blood when you are injured. Normally, your body will dissolve the clot once your injury has healed.