The Fascinating World of Haemostasis and Thrombosis Susan Louw

Disease processes Abnormal clotting Abnormal bleeding

Bleeding Disorders Vessel wall / Vascular Disorders Platelets Coagulation factors

Vascular Disorders Inherited Acquired Hereditary Haemorrhagic Telangiectasia Connective Tissue disorders Acquired Simple benign bruising Senile purpura Scurvy Steroid purpura

Hereditary Haemorrhagic Telangiectasia

Platelet Disorders – Q & Q: Quantity Failure of production (Bone Marrow failure) Increased destruction ITP Drug related Infections TTP DIC Splenomegaly

Idiopathic Thrombocytopenic Pupura (ITP) Chronic (women 15-50yrs) and Acute (children) Idiopathic or secondary (HIV!, SLE, viral infections etc.) Platelet sensitisation with auto-antibodies with premature removal by spleen

Idiopathic Thrombocytopenic Pupura (ITP) Clinically: Mucocutaneous bleeding

Idiopathic Thrombocytopenic Purpura (ITP) Diagnosis Plt count 5 – 50 x109 /L on FBC with increased megakaryocytes on bone marrow biopsy Treatment Corticosteroids Splenectomy etc. etc.

Platelet Disorders – Q & Q: Quality Hereditary Glanzmann’s Thrombasthenia Bernard-Soulier syndrome Storage pool disease Acquired Anti-platelet drugs Uraemia Myeloproliferative and –dysplasic disorders

Platelet Disorders – Q & Q: Bernard-Soulier Disease:

Bernard-Soulier Disease: Qualitative and Quantitative abnormality of platelets Large platelets Congenital deficiency of Glycoprotein 1b on platelet surface Reduced platelet numbers

Anti-Platelet DRUGS

Anti-Platelet DRUGS Aspirin: cyclo-oxygenase inhibitor Clopidogrel: blocks ADP receptors Abxicimab: GPIIb/IIIa inhibitors

Diagnosis of Platelet Disorders FBC and Diff BMAT Bleeding time Platelet aggregation studies

HEREDITARY Coagulation Factor defect Haemophilia A: defective or reduced FVIII Haemophilia B: defective or reduced FIX Von Willebrand’s disease: defective or reduced vWF

HEREDITARY Coagulation Factor defect Mode of inheritance: Haemophilia A: Sex linked Haemophilia B: Sex linked Von Willebrand’s disease: Autosomal dominant

HEREDITARY Coagulation Factor defect Treatment Factor replacement – BUT then there was….

HEREDITARY Coagulation Factor defect Treatment Factor replacement Viral inactivation Recombinant production DDAVP Supportive measures Gene therapy… watch this space

Thrombotic disorders Hereditary Acquired Deficiencies of natural anticoagulants Antithrombin / Protein C / Proten S Acquired Post surgery Post delivery Long distance travel Immobilisation

Rudolf L.K. Virchow (1821-1902)

Virchow’s Triad

Thrombotic disorders

Warfarin and its partner Reasons for warfarin therapy Many !!!! Prevent clot formation Prothrombotic state Inherited or Acquired Life saving Side-effect: Bleeding

The Other Partner Heparin