Haemostasis II

Question 1

Bleeding causes

Answer 1

Vascular disorders

Platelet disorders: Thrombocytopenia & defective function

Defective coagulation: Inherited
& acquired

Question 2

Pattern of bleeding

Answer 2

Depends on aetiology:

Vascular and platelet causes
Bleeding into mucous membranes and skin

Coagulation disorders
Bleeding into joints and soft tissues

Question 3

Vascular bleeding definition & causes

Answer 3

Problems with vessel wall

Inherited:
Hereditary haemorrhagic telangiectasia
Ehlers-Danlos syndrome

Acquired:
Scurvy, steroids, senile

Question 4

Thrombocytopenia (low platelets) definition & causes

Answer 4

Normal range 150-400 x 109/L
Thrombocytopenia – plts < 150
Symptoms when plts < 10
Epistaxis, GI bleeds, menorrhagia, bruising

Inherited causes (rare)
Acquired (common) eg: ITP, drug-related, DIC

Question 5

ITP = immune thrombocytopenia

Answer 5

Treat with steroids or intravenous immunoglobulins

or occasionally splenectomy

Question 6

Platelet function disorder causes

Answer 6

Platelet count – normal or low

Inherited:
Many rare diagnoses, eg: Glanzmann’s

Acquired:
Drugs eg: Aspirin, NSAIDs

Question 7

Coagulation disorder definition

Answer 7

Due to a defect in the coagulation cascade

Inherited (rare)

Acquired (common)

Question 8

Haemophilia overview

Answer 8

Haemophilia A – deficiency of factor VIII
Haemophilia B – deficiency of factor IX
(also known as Christmas disease)

Both X-linked conditions affecting males only

Clinical features:

Spontaneous bleeding into joints and muscle
Unexpected post-operative bleeding
Chronic debilitating joint disease
Family history in majority of cases

Question 9

Coagulation tests

Answer 9

APTT = activated partial thromboplastin time
Assesses the intrinsic pathway

PT = prothrombin time
Assesses the extrinsic pathway

TT = thrombin time
Fibrinogen level
Factor level assay
Bleeding time

Question 10

Haemophilia diagnosis

Answer 10

Prolonged APTT
tests factors VIII, IX, XI, XII in the intrinsic pathway

Normal PT
tests factors II, V, VII, X in the extrinsic pathway

Low factor VIII or IX levels
<1% = severe; 1-5% = moderate; >5% = mild

Question 11

Haemophilia treatment

Answer 11

Historic treatments – fractionated human plasma

HIV and Hepatitis C infection (and risk of vCJD)

Current treatment – infusions of recombinant factor VIII or factor IX to 50-100% of normal

Prophylactic treatment has revolutionised management of haemophilia patients

Question 12

von Villebrand disease overview

Answer 12

Autosomal dominant

von Willebrand factor = large multimeric protein that carries factor VIII in the blood

vWF also binds platelets to endothelial collagen

vWD = deficiency of vWF and FVIII in plasma

Mucocutaneous, nosebleeds, menorrhagia

Question 13

vWD tests

Answer 13

Prolonged APTT
Normal PT
Low vWF level/function
Low factor VIII level
Prolonged bleeding time
Defective platelet function

Treatment with desmopressin (DDAVP), anti-fibrinolytics and plasma products

Question 14

Acquired coagulation disorders

Answer 14

These are non-inherited causes of “haemophilia”

Liver disease
Defects in synthesis of clotting proteins
Impaired platelet function and fibrinolysis

Disseminated intravascular coagulation (DIC)
Release of pro-coagulant material into circulation
Causes both bleeding and thrombosis to occur

Question 15

Meningococcal DIC

Answer 15

Prolonged PT, APTT, TT
Low fibrinogen, low platelets
Raised D-dimers or FDPs

Question 16

Anti-coagulant drugs

Answer 16

Iatrogenic – overdose of anti-coagulant drugs

Heparin – used to treat MIs, PEs, DVTs

Warfarin – used to treat PEs, DVTs, AF, prosthetic valves

DOACs (formerly NOACs) = direct (novel) oral anti-coagulants

Direct thombin inhibitors (dabigatran, argatroban)

Factor Xa inhibitors (rivaroxaban, apixaban)

Question 17

Vitamin K deficiency

Answer 17

Vitamin K is required for gamma-carboxylation of factors II, VII, IX, X

Inhibited by warfarin (monitored using the INR)

Deficiency of vitamin K due to:
Malabsorption of vitamin K
Biliary obstruction (jaundice)
Haemorrhagic disease of the newborn (give 1mg at birth)

Question 18

Coagulation cascades

Answer 18

Extrinsic – factors II,V,VII,X, monitor by PT

Intrinsic – other factors (inc. VIII + XI) monitored by APTT

Both pathways result in a “thrombin burst” that produces a blood clot and haemostasis