Week 2 part 2 Flashcards
Disseminated intravascular coagulation
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
Disseminated intravascular coagulation causes
Infection Malignancy Trauma e.g. major surgery, burns, shock, dissecting aortic aneurysm Liver disease Obstetric complications
Management of Disseminated intravascular coagulation
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
Disseminated intravascular coagulation features
Clinically bleeding is usually a dominant feature, bruising, ischaemia and organ failure
Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products
Blood tests in Disseminated intravascular coagulation
Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products
Immune thrombocytopenic purpura (ITP)
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.
Features of Immune thrombocytopenic purpura (ITP)
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
Immune thrombocytopenic purpura (ITP) management
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
Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
Acquired causes of Platelet Functional Defects
Drugs (eg Aspirin, non-steroidal anti inflammatory drugs)
Renal failure
Von Willebrand’s disease
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.
Causes of acquired Thrombocytopenia
Marrow failure
Peripheral destruction
Commonest cause of primary haemostatic failure
Thrombocytopenia
von Willebrand factor
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
Investigations for Von Willebrand’s disease
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Von Willebrand’s disease management
- 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
Type 3 von Willebrand’s disease
(most severe form) is inherited as an autosomal recessive trait. Around 80% of patients have type 1 disease
total lack of vWF (autosomal recessive)
Type 1 Von Willebrand’s disease
type 1: partial reduction in vWF (80% of patients)
Type 2 Von Willebrand’s disease
abnormal form of vWF present
Hemophilia
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)
Features of hemophilia
haemoarthroses
haematomas
prolonged bleeding after surgery or trauma
Investigations in hemophilia
prolonged APTT
bleeding time, thrombin time, prothrombin time normal
Multiple clotting factor deficiencies
examples
Disseminated Intravascular Coagulation
Liver failure
Vitamin K Deficiency/Warfarin therapy
Where are coagulation factors produced?
All coagulation factors are synthesised in hepatocytes
Reduced in liver failure
What coagulation factors require carboxylation by Vitamin K for their function?
Factors II, VII, IX & X are carboxylated by vitamin K which is essential for function
Sources of Vitamin K
Diet
Intestinal synthesis
Absorbed upper intestine
Requires bile salts for absorption
Causes of Vitamin K Deficiency
Poor dietary intake Malabsorption Obstructive jaundice Vitamin K antagonists (warfarin) Haemorrhagic disease of the newborn
Haemophilia A
Haemophilia A (factor VIII deficiency)
Haemophilia B
Haemophilia B (factor IX deficiency)
Single Factor Deficiency examples
Haemophilia A and B
Isolated prolonged APTT
Thrombotic Events
Arterial = Coronary, cerebral, peripheral
Venous = Deep venous thromboses, Pulmonary Embolism
Arterial thrombosis
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.
Management of Arterial thrombosis
Blood-thinning medicines (anticoagulants)
Catheters
Stents
Medicines to interfere with or dissolve blood clots
Venous thromboembolism: risk factors
increased risk with advancing age obesity family history of VTE pregnancy (especially puerperium) immobility hospitalisation anaesthesia central venous catheter: femoral >> subclavian
What medications increase the risk of Venous thromboembolism?
combined oral contraceptive pill
raloxifene and tamoxifen
antipsychotics (especially olanzapine)
Venous thrombosis
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.
Virchow’s triad
Stasis
Vessel wall damage
Hypercoagulability
Venous thrombosis management
Heparin/warfarin/New oral anticoagulants (e.g. rivaroxiban)
Deep Vein Thrombosis features
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
Potential features of pulmonary embolism include:
chest pain - typically pleuritic dyspnoea haemoptysis tachycardia tachypnoea respiratory examination - classically the chest will be clear
Management of PE
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
Hypercoagulability CAUSES
Associated with release of tissue factor, raised VWF and factor VIII
Causes of inherited thrombophilia
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
Hereditary Thrombophilias
A group of genetic defects in which affected individuals have an increased tendancy to develop premature, unusual and recurrent thromboses.
Consider Hereditary Thrombophilia Screening
Venous thrombosis <45 years old Recurrent venous thrombosis Unusual venous thrombosis Family history of venous thrombosis Family history of thrombophilia
Causes of acquired Thrombophilia
Antiphospholipid syndrome
Drugs - the combined oral contraceptive pill
Management of Hereditary Thrombophilia
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
Risk factors for Recurrent Thrombosis
History of previous thrombosis
Spontaneous thrombosis rather than acquired transient risk factor (eg immobility or surgery)
Family history
Antiphospholipid syndrome
Is an acquired thrombophilia Multi organ disease Arterial and venous thromboses Recurrent fetal loss Mild thrombocytopenia
Investigations of Antiphospholipid syndrome
Either Lupus anticoagulant or Anti cardiolipin antibodies
APTT usually prolonged
Antibodies may be elevated following surgery, drugs or malignancy
Management of Antiphospholipid syndrome
Need anticoagulation with INR between 3 and 4 (warfarin and aspirin)
Conditions associated with Antiphospholipid Antibodies
Autoimmune Disorders
Lymphoproliferative Disorders
Viral Infections
Drugs
Complications of thrombosis
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.
Risk factors for arterial thrombosis may include:
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
Venous thrombosismay be caused by:
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
D-dimer
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.
