Bleeding Disorders

Front 1

What are the primary components involved in forming a blood clot in the vessel wall?

Back 1

Von willerbrand factor, collogen, tissue factors (X, VIII), platelets, thrombin, fibrin

Front 2

What is the first step to approaching a patient who is suspected to have a bleeding disorder?

Back 2

Do a full bleeding history:

What is the pattern of bleeding? - Bruising inappropriately, lots of nose bleeds,

Post surgical bleeding? (if they don't bleed a lot after surgery then they are unlikely to have a bleeding disorder)

Menorrhagia? - very common in vWF disease

How appropriate is the bleeding? - e.g do they get a massive heamotoma after a small injection, massive bruise if somebody prodded them ect.

Is it congenital or acquired? - age at first event, if there is no history of bleeding problems in the notes then likely acquired

Front 3

What is the difference in the pattern of bleeding between platelet related bleeds and coagulation related bleeds?

Back 3

Platelet deficiency bleeds - mucosal bleeding, recurrent epistaxis, Purpura, Menorrhagia, GI

Coagulation related bleeds - articular surface between joints, muscle, CNS

*Basically - Platelet bleeds create more outward bleeds, visible bleeding. Coagulation are more internal.*

Front 4

What physical clinical signs would you look for in a patient you suspect to have a bleeding disorder?

Back 4

Petechia rash - red rash on the surface of the skin , caused by burs capillaries on the surface. When pressed they don't blanch! (if it was a normal spot it would blanch because the vessel is intact and so once you release pressure the blood would flow back in, in patients with blood disorders the blood has all leaked out to the surface so just remains there even if you just press in on it)

Swollen joints - particularly in people with Haemophilia, due to articulating joints rubbing against internal vessels and causing bleeds

Reduced muscle bulk around joints - blood from swollen joints seeps into surrounding muscles and causes atrophy.

Multiple visible bruising

Front 5

What is the most common cause of death in those with Haemophilia?

Back 5

Inter-cranial Haemorrhage

Front 6

What type of genetic disorder is Haemophilia A&B?

Back 6

Both Haemophilia A&B are X-Linked Recessive disorders.

Means women have 1 in 2 chance of being carriers and have 1 in 2 chance of having affected son.

Front 7

What type of Haemophilia is more common?

Back 7

Haemophilia A affects about 1 in 10,000

(haemophilia less common - affects about 1 in 60,000)

*both have identical phenotypes so present the same*

Front 8

What are the main clinical features of haemophilia?

Back 8

Typically first presents in young boys

Haemathorosis - bleeding into joint spaces (main joints affected are the hinge joints e.g knees, ankle, elbows)

Muscle haematoma

CNS bleeding

Retroperitoneal bleeding

Post surgical bleed

Front 9

What is the common bone disorder that can arise as a result of joint swelling in haemophilia?

Back 9

Haemophilic arthropathy - joint degradation due to blood build up.

When they bleed into the joint - the macrophages go in and gobble up the red cells and theion which creates inflammation and dense synovial inflamtion filled with cytokines. Thecytokines then eat away at the joint space and errode into the bone.

Front 10

Beyond Haemophilic arthropathy, what are the other clinical complications that can arise as a result of the bleeding in Haemophilia?

(clue: mainly MSK related)

Back 10

Synovitis (blood irritates the synovial fluid)

Neurovascular compression (compartment syndrome due to blood build up putting pressure on muscles causing deoxygenation)

Stroke

Inter-cranial Haemorrhage

Front 11

What tests would you perform to confirm a diagnosis of Haemophilia?

Back 11

If severe patient Clinical History should be enough and FH e.g Mums dad had haemophilia, onset 6 to months, male

Prothrombin Time (PT) aka INR - coagulation test, measures the extrinsic and common pathways of coagulation reported as the INR

Factor VIII - should be reduced

APTT - Activated partial thromboplastin time: screens plasma for abnormalities in factors of intrinsic and common pathways

Fibrinogen levels

Genetic analysis

Front 12

What is the treatment for Haemophilia?

Back 12

Coagulation factor replacement - Factor VIII/IX

(obtained from plasma which is fractionated through chromatography)

DDAVP (Decompressin) = Increase plasma levels on vWF, factor VIII and t-PA so their coagulation by about 4 times

Tranexamic Acid–helps to stabliseclot by inhibiting bodies natural fibrionlysis

*most of these are prophylaxis based trying to prevent the complications before they arrise*

Front 13

What are the treatments for Haemophilia once the affects have already mounted and the condition has become chronic? -i.e prophylaxis not used in time

Back 13

Once Haemophilia has take its tole on the body supportive treatment is necessary:

Splints

Physiotherapy

Synovectomy –helpful becauseof joint destruction

Joint replacement

Front 14

What are the complications with the coagulation and DDAVP therapy used to treat Haemophilia?

Back 14

The biggeestside effeectof treatment is the development of coagulation inhibitors.

The development of anti factor VII antibodies -theimmune system recognise the protein as foreign and so antibodies are developed agaisnt it – the see it bind to it and stop it fromworking making the treatment futile.

The main side effects for DDAVP therapy is MIs and Hypoatreamia (low Na levels) because the plasma has been diluted down with all the things that have been added to it.

Lowered immune and so increased risk to viral infections - e.g HIV, HBV, HCV

Front 15

What is Von Willerbrands Disease?

Back 15

Hereditary deficiency of von Willerbrand's factor (vWF) which causes platelet dysfunction

Autosomal dominant disorder

Common - 1 in 200

*it is often a quantitive (type 1) or qualitative (type 2) problem - e.g there is not enough of the protein or it is there but just not working properly*

Front 16

What is the most common bleeding disorder?

Back 16

Von Willerbrands diesese

Front 17

What type of bleeding occurs in Von Willerbrands disease? Platelet or Coagulation?

Back 17

Von Willerbrands is a platelet type disorder - therefore bleeding is often external e.g Mucosal bleeding, nose bleeds, heavy periods

Front 18

What are the symptoms of Von willerbrands disease?

Back 18

Easy bruising

Bleeding gums

Nose bleeds

Heavy periods

*bleeding into joints and other severe bleeding affects are not common*

Front 19

What is the treatment for Von willerbrands disease?

Back 19

Treated ONLY IF they are actively bleeding all the time or about to go under the knife:

Repalacement of vWF

Decpompressin DVAPP - Desmopressin (DDAVP) stimulates the release of von Willebrand factor (vWF).

TranexamicAcid = Anti-fibronlytic

Front 20

What is the most common type of acquired bleeding disorder?

Back 20

Thrombocytopenia

Front 21

Beyond Thrombocytopenia, what are other causes for acquired bleeding disorders?

Back 21

Liver failure

Renal failure

Drugs - warfarin, aspirin, heparin, clopidogrel, riveroxaban

Front 22

What is thrombocytopenia and what is the aetiology behind it?

Back 22

Condition causing low platelet count.

Low platelet count is either due to decreased production or increased consumption.

Decreased production of platelets due to marrow failure and hypoplasia (under production of products)

Increased consumption could be due to auto-immunity or Disseminated intravascular coagulation (DIC) - DIC often caused by trauma, sepsis, burns, malignancy

Front 23

What are the clinical signs of thrombocytopenia?

Back 23

Petechia Rash - most commonly found on the legs because most blood flows here

Ecchymosis - a discolouration of the skin resulting from bleeding underneath typically caused by bruising

MucosalBleeding

Occasional but rare CNS bleeding

*blood blisters on tongue and palate are typical of thrombocytopenia*

Front 24

What is the difference between Thrombocytopenia and Immune Thrombocytopenia (ITP)?

Back 24

Thrombocytopenia is associated with systemic disease e.g bone marrow failure, or DIC - sepsis ect. causing destruction of platelet cells

vs.

Immune thrombocytopenia is when auto antibodies against platelets are triggered by infection - e.g EBV, HIV and Lymphoma

Front 25

What infections are associated with triggering Immune thrombocytopenia where auto antibodies begin to destroy the bodies platelets?

Back 25

EBV

HIV

Lymphoma

Front 26

What on a blood test indicates that a patient has thrombocytopenia?

Back 26

If the only thing abnormal on the blood test is Platelets and they are low then it is probably Thrombocytopenia

Front 27

What is the treatment for Thrombocytopenia?

Back 27

Treat the cause:

If infection or autoimmune then Steroids or immunosuppressants

also treat with...

Thrombopoietin - workby enhancing platelet production in the marrow.

Front 28

Why does liver failure lead to bleeding disorders?

Back 28

Liver failure can lead to bleeding disorders because the liver is responsible for making clotting factors.

So if dysfunctional then these factors aren't made as much and so the range of balance for heamostasis is much thinner (this is why those with liver disease can also experience coagulation disorders).

And it stores Vit K which a lot of factors are dependant on.

*associated with symptoms of spontaneous variceal bleeding from organs e.g Osophageal varices due to portal hypertension*

Front 29

Which coagulation factors are dependant on Vitamin K?

Back 29

Factors dependent on Vit K:

II, VII, IX, X

Front 30

What is the name of the disease in which newborns have bleeding at birth due to lack of Vit K?

Back 30

Haemhorrhagic disease of the new born - can lead to massive cranial haemorrhage.