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 : 150-450 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: vonWillebrandts disease , Bernard-Soulier syndrome acquired: uremia

defects of platelet aggregation

inherited: Glantzmanns 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

systemic inflammation malignancy iron deficiency hemorrhage postsplenectomy

Secondary (reactive) thrombocytosis

Thrombocytopenia (1)
Decreased marrow production of megakariocytes congenital disorders
thrombocytopenia with absent radii (TAR) Fanconis 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

splenectomy permanent responses - 60% immunosuppresive drugs intravenous immunoglobulins other - danazol, antiRhD