Haemostasis

Tiffany Shaw

MBChB II

2002

Haemostasis Pathway

Injury

Collagen exposure Tissue Factor

Platelet adhesion Coagulation Cascade

Release reaction

Platelet aggregation Fibrin

Primary haemostatic plug

Secondary haemostatic plug

Coagulation Cascade

Integrity of Haemostasis

Depends on:

1. Vessel wall

2. Platelets (no. and function)

3. Coagulation factors

Vessel Wall

• Release tissue factor that initiates coagulation cascade.

• Exposed collagen results in platelet adhesion (using vWF as a bridge).

• Hereditary haemorrhagic telangiectasia • Scurvy• Senile purpura

Hereditary Haemorrhagic Telangiectasia

Low Platelet Number

• N = 150 – 450• Excessive bleed / Spontaneous bleed• Mucosal surfaces / Skin

• Immune Mediated Thrombocytopenia• Drug induced• Haemolytic Uraemic Syndrome• DIC

Platelet Dysfunction

• Abnormal platelet aggregation

• Normal platelet count

• Excessive / spontaneous bleed

• Mucosa / Skin

• Inherited disorders

• Drug induced

Eccymoses

Coagulation Factors Deficiency

• Spontaneous bleeding into deep tissues• Increased post-traumatic haemorrhage• Factor 8 – Haemophilia A• Factor 9 – Haemophilia B• vWF – Von Willebrand’s disease

Von Willebrand’s Factor:• Protein produced by endothelial cells which mediates

platelet adhesion to endothelium and carries factor 8 in plasma.

Haemaphilia A

• Factor 8 deficiency

• 50 / million people

• Sex-linked

• Most detected in childhood

• Mild symptoms ~ spontaneous bleed

• Chronic joint disease after repeated bleed

Haemophilia B

• Factor 9 deficiency

• = Christmas disease

• Also sex-linked

• Similar presentation as haemophilia A

• Much rare

Haemoarthroses

Von Willebrand’s Disease

• vWF deficiency

• Autosomal dominant (F = M)

• Most common inherited bleeding disorder

• Bleeding from mucosa

• Excessive blood loss in trauma

• Bleeding into deep tissue (rarer)

Liver Disease

• Mixed – both coag deficiency and platelet problem

• Reduced coag factor synthesis

(1, 2, 5, 7, 9, 10)

• Cirrhosis Hypersplenism Thrombocytopenia

DIC

Generalised activation of coag cascade

Wide-spread fibrin formation

Thrombosis Low coag factor

Bleeding

DIC

Consequence of Thrombosis:1. Tissue infarction Renal impairment2. CVA3. PE4. DVT

Consequence of Bleeding:1. Purpura2. GI Bleed

DIC

Causes of coag cascade activation:

1. Sepsis2. Disseminated cancer3. Obstetric complications (e.g. retained product of

conception)4. Fulminant liver disease5. Anaphylaxis6. AML

Drug Induced Coag Factor Def

Heparin:

• Inactivates certain coag factors (e.g. 9a, 10a, 11a, 2)

• Also impairs platelet function

Warfarin:

• Block synthesis of Vit K dependent factors (2, 7, 9, 10)

Other Disorders

• Vitamin K deficiency

• Autoantibodies to coag factors

• Haemorrhagic disease of the newborn

• Massive transfusion

Investigations for Bleeding

1. Platelet Count

2. Bleeding time

3. Activated Partial Thromboplastin Time

4. Prothrombin Time (INR)

5. Plasma level assay

Investigations for BleedingCondition TestWall Defect All tests are normal.

Low Platelet Low platelet count + bleeding time

Platelet Dysf Normal platelet count + bleeding time

Haemophilia APPT + Plasma level

vWD APPT + bleeding time + plasma level

Liver Disease INR + APPT + platelet count

Drug Induced INR + APPT + plasma level

DIC All tests are abnormal.

Management

1. Replace deficiency

2. Treat underlying cause

3. Reversal of drug effects

4. Supportive therapy

Extra Notes on ITP

• Platelets become coated by autoantibodies• Removed by RES reduced lifespan• Low platelet count• Acute / Chronic• Purpura / Spontaneous bleed /

Asymptomatic• May resolve spontaneously or require

medical treatment

Extra Notes on ITP

• Isolated low platelet count

< 20

• Increased megakaryocytes in bone marrow

• Normal INR + APPT

• Increased bleeding time

Extra Notes on ITP

Mx:

1. Do nothing

2. Prednisolone

3. Splenectomy

4. Other immunosuppresives

Extra Notes on IPT

May be associated with:

• Haematological malignancies

• Viral infections (e.g. HIV)

• C.T. disorders (e.g. SLE)

Test for c.t. disorders.

70-Year-Old with ITP

• Incidental finding in 1993

• Platelet count = 60

• Asymptomatic

• Referred to haematologist

• Test for c.t. disorders

• U/S for spleen size

• Bone marrow biopsy

70-Year-Old with ITP

• Negative for c.t. disorders

• Spleen size normal

• Bone marrow: increased megakaryoccytes

• Continue monitoring (weekly FBC)

70-Year-Old with ITP

• December 1993

• Bruising with minimal trauma

• Platelet count = 43

• Start Prednisolone

• After 6/52 platelet count 190

• Slowly dropped again after withdrawal

• Asymptomatic

70-Year-Old with ITP

• Continue monitoring

• Platelet transfusion if serious bleeding occurs

• Consider splenectomy if worsens

• Discharged to GP last week