Haematology Dr Khudhair Abass Ali College of Medicine – Baghdad University

Objectives Lecture 2 1.Thrombotic thrombocytopenic purpura. 2.Thrombocytosis. 3.Platelets function disorders. 4.Vessel wall abnormalities. Hereditory haemorrhagic telengiectasia. Henoch shonlein purpura.

Thrombotic Thrombocytopenic Purpura (TTP) (HUS) Aetiology : Autoimmune disorder, mediated by Abs. against ADAMTS – 13 enzymes. (This enz. normally clears VWF multimers to produce normal functional units and its deficiency results in large VWF multimers which cross – link platelets and leads to microvascular occlusion by plat. Thrombi e.g. brain, kidney). Idiopathic, associated with drugs (Ticlopidine, Ciclosporine), HIV, Malignancy. Clinically : Sporadic, Fluctuating, Familial: reported, F > M, young – adolescent 1. Fever 2. Anemia : Microangiopathic haemolytic (Fragmented RBCs), ↑ Reticulocyte count, Jaundice, ↑ LDH, -ve coomb’s test. 3. Thrombocytopenia – Purpura, count usually < 20 X 10 9 /L 4. Neurological: Convulsion, Coma, Paralysis ( Transient or prolonged), Psychological. 5. Renal : intermittent proteinuria, Renal Failure (more in HUS) Lecture (2)

Lab. ↑ WBC, ↓ plat. PT, PTT Normal B.M Normal or increase cellularity Gingival Biopsy – Helpful DD : ITP Prognosis : 10% Recurrent. Untreated – 90% Mortality in 10 days Treated – Mortality 20-30% at 6 months Sudden death due to cardiac Micro thrombi Treatment : Plasmapharesis with FFP 12 bags/day for weeks – Months Corticosteroids, Rituximab have a role. Pregnant – May needs termination if no response

Plat. Function disorders 1. Acquired a. Iatrogenic Aspirin – Cyclo – Oxygenase inhibitor Clopidogrel – ADP receptor inhibitor Abciximab – Gp 11 b / 111 a inhibitor Tirofiban – Gp 11 b / 111 a inhibitor Dipyridamol – phosphodi esterase inhibitor b. Antibiotics: Penicillin, Cephalosporines c. Heparin d. CRF e. Myelofibrosis f. Paraproteinaemia g. CTD

2. Congenital a. Glanzmann’s thromboasthenia - Def. of GP 11b / 111a AR, bleeding variable, often severe. b. Bernard – Soulier dis. def. of GP 1b. AR c. Defective plat. Granules – deficiency of dense granules (b & c cause mild bleeding e.g. after trauma or surgery, rarely spont.) Management : Local mechanical pressure. Antifibrinolytic e.g. Tranexamic acid may be useful. Plat. Transf. in severe bleeding. Recombinant FVIIa in resistant bleeding in Glanzmann's.

VESSEL WALL ABNORMALITIES 1. Hereditary: HHT, EDD, Osteogenesis imperfecta 2. Inflammatory: Bacterial, Viral, Vasculitis. 3. Abn. Collage: Senile, Scurvy, Steroids. 4. Metabolic : Liver disease, Renal, Amyloidosis. 5. Others: Factitious, Paraproteinaemia, Drugs. Hereditary Haemorrhagic Telengiectesia (HHT) (Osler – Rendu – Weber synd.) Clinically := A.D., Telengiectasia and small aneurysms on Fingers, lips, Face, Tongue, Nasal passages, Lungs, G.I.T. / Usually appear at adulthood. Signif. No. have Pulmonary. A.V. malformation (PAVMS) → Arterial Hypoxaemia due to Rt. To It. Shunt → paradoxical embolism → stroke or cerebral abscess. Recurrent Bleeding e.g. Epistaxis or Malaena → Fe def. An. Treatment : Deficult because. Of multiple Bleeding sites. Regular Fe therapy Local Cautary or Laser, Oestrogens ?

Ehlers – Donalos Dis : AD., Collagen defect Fragile Bl. Vessel. And organ membrane. → Bleeding and organ rupture Joint Hypermobility Scurvy. Vitamin C def. → affect normal synthesis of collagen. Perifollicular and patechial haemorrhage, sub- periosteal bleeding. Diagnosis : Dietary History

Henoch – Schonlein Purpura (HSP). Children and young adults.. Immune complex deposition in small vessel. With vasculities. Often preceded by upper resp. inf. Clinically : 1. Purpura: (raised) Buttocks and legs 2. Abdominal colicky pain and bleeding 3. Arthritis : Knees, Ankles. 4. Nephritis : 40% (May be later – 4 wks.) Diagnosis : Clinical, Tissue biopsy ( IgA deposition in bl. Vessel.) Prognosis : good, Adverse if HTN, RF, Proteinuria > 1.5 g / day Treatment : Nonspecific Steroids for joint or GI involvement Nephritis – pulse iv steroids ± immunosuppressors.

Thrombocytosis 1. Reactive (most Common) 2. Clonal a. Chr. Infl. Dis. E.g. ulc. Collitis a. Pri. Thrombocythaemia (ET) b. CTD e.g. Rh. Arthritis. b. PRV c. Malignancy e.g. Hodgkin’s dis. c. Myelofibrosis. d. Acute Haemolysis d. CML. e. Fe. Def. An. e. MDS. f. GI bleeding g. Post – splenectomy Clinically : Those of the underlying dis. Haemostasis rarely affected PRV, ET, Myelofibrosis, may present with thrombosis and rarely bleeding Reactive : No splenomegally.

Summary TTP Autoimmune. Clinically: 1.Fever 2.Microangiopathic haemolytic An.(Fragmented RBC) 3.Low plat. 4.Neurological. 5.Renal. R : FFP + Plasmapharesis. Thrombocytosis: Reactive or clonal. Platelet function disorders: Acquired or congenital. Vessel wall abnormalities : HHT, HSP