Hemostatic System - general information Normal hemostatic system –vessel wall –circulating blood platelets –blood coagulation and fibrynolysis Platelets –disc-shape cells –arise from megakariocytes in bone marrow –1/3 of platelets are sequestrated in the spleen –other 2/3 circulate for 7-10 days –are responsible for primary hemostasis –normal platelet count : G/l

Bleeding Diathesis Is caused by inherited or acquired defects of –vessel wall –platelets number and/or function –coagulation system Is charcterised by –spontaneous bleeding –extensive bleeding after minimal trauma

Platelets Disorder Disorder of platelet number –thrombocytopenia –thrombocytosis Disorder of platelet function

Disorder of platelets function defects of platelet adhesion –inherited: vonWillebrandt’s disease, Bernard-Soulier syndrome –acquired: uremia defects of platelet aggregation –inherited: Glantzmann’s thrombasthenia –acquired: dysproteinemia, drug ingestion (ticlopidin) defects of platelet release –inherited: grey-platelet, Hermansky-Pudlak,Chediac-Higashi syndr. –acquired: cardiopulmonary bypass, myeloproliferative disorders, drugs

Thrombocytosis Thrombocytosis resulting from myeloproliferation –essential thrombocythemia –polycythemia vera –chronic myelogenous leukemia –myeloid metaplasia Secondary (reactive) thrombocytosis –systemic inflammation –malignancy –iron deficiency –hemorrhage –postsplenectomy

Thrombocytopenia (1) Decreased marrow production of megakariocytes congenital disorders –thrombocytopenia with absent radii (TAR) –Fanconi’s anemia –May-Hegglin anomaly acquired disorders –marrow infiltration with malignant cells –marrow fibrosis –aplastic and hypoplastic anemias ( idiopathic, drugs, toxins ) –deficiency states ( vitamin B12, folate, iron ) –paroxysmal nocturnal hemoglobinuria

Thrombocytopenia (2) Splenic sequestration of circulating platelets splenic enlargement due to tumor infiltration splenic enlargement due to portal hypertension

Thrombocytopenia (3) Increased destruction of circulating platelets congenital disorder –Wiscott-Aldrich syndrome, Bernard-Soulier syndrome acquired disorders nonimmune destruction –vascular prostheses, cardiac valves –DIC –hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura –sepsis immune destruction –idiopathic thrombocytopenic purpura ( ITP ) acute and chronic –drug-induced thrombocytopenia –chronic autoimmune disorders –infection (HIV) –malignancies

Platelets Disorder - signs and symptoms asymptomatic if platelets count > 50 G/l onset of bleeding after trauma - immediate site of bleeding - superficial: skin, mucous membranes, nose, genitourinary tract physical finding - petechiae, ecchymoses

Idiopathic Thrombocytopenic Purpura (1) the most common cause of isolated thrombocytopenia autoimmune disease with antiplatelet antibodies and shortened platelets life span forms of ITP acute ITP –children (90% of pediatric case of immune thrombocytopenia) – preceded by viral infection –spontaneous recovery within 4-6 weeks in 60% of patients chronic ITP –20-40 years –women predominance F:M=3:1

Idiopathic Thrombocytopenic Purpura (2) Clinical features –petechiae –ecchymoses –mucose membranes bleeding –menorrhagia –rare internal, intracranial bleeding Diagnosis –platelet count <100G/l –bleeding time - usually normal –peripheral blood smear - large platelets –bone marrow examination - normal or increased number of megakariocytes –antibodies against Gp IIb/IIIa –shortened platelet survival

Treatment of ITP not necessary unless platelets count > 20G/l or there is extensive bleeding corticosteroids permanent responses - 30% –prednisone 1mg/kg for 4-6 weeks splenectomypermanent responses - 60% immunosuppresive drugs intravenous immunoglobulins other - danazol, antiRhD