Hematology Lecture Notes PDF

Hematology Lec 12&13 (Haemostasis 1) Dr Sura Al Shamma Pathology department Hemostasis The term hemostasis means prevention of blood loss Whenever a vessel is injured ,by formation of plug(clot)and keeping blood fluidity at the same time. Haemostasis Important balance between pro...

Hematology Lec 12&13 (Haemostasis 1) Dr Sura Al Shamma Pathology department Hemostasis The term hemostasis means prevention of blood loss Whenever a vessel is injured ,by formation of plug(clot)and keeping blood fluidity at the same time. Haemostasis Important balance between procoagulant and anticoagulant mechanisms 5major components Blood vessels Platelets Coagulation factors Coagulation inhibitors Fibrinolysis Events of haemostasis Hemostasis is achieved by several events : (1) vascular constriction (spasm) (2) Formation of a platelet plug, -Primary hemostasis (3) Formation of a blood clot as a result of blood coagulation, (secondary hemostasis). (4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently. And then retraction of the clot to prevent propagation of the thrombus Normal Haemostasis Disorder of hemostasis Disorder of hemostasis Generally, is classified into: A-Bleeding disorders. B-Thrombotic disorders  Haemostasis anticoagulant procoagulant anticoagulant procoagulant anticoagulant procoagulant Tests of hemostatic function A number of simple tests are employed to assess the platetlet, vessel wall and coagulation components of haemostasis 1. CBC- Blood count and blood film examination : As thrombocytopenia is a common cause of abnormal bleeding, patients with suspected bleeding disorders should initially have a blood count including platelet count and blood film examination. 2. Screening tests of blood coagulation (PT ,PTT,TT) Screening tests provide an assessment of the ‘extrinsic’ and ‘intrinsic’ systems of blood coagulation and also the central conversion of fibrinogen to fibrin. PT-prothrombin time PTT-partial thrombin time. TT-Thrombin time Screening test for coagulation ‫مهم جدا‬ Coagulation pathway Tests of haemostatic function -cont 3. Specific assays of coagulation factors 4. Bleeding time 5. Tests of fibrinolysis 6. Tests of platelet function Bleeding Disorders Bleeding disorders are a group of disorders that share the inability to form a proper blood clot. They are characterized by extended bleeding after injury, surgery or trauma. Sometimes the bleeding is spontaneous, without a known or identifiable cause.  Bleeding disorders Causes of bleeding -Abnormal bleeding may result from: Vascular disorders Platelet disorders (thrombocytopaenia, abnormal function) Defective coagulation Combination of the above factors Pattern of bleeding Vascular and platelet disorders-mucous membrane and skin; petechiae and purpuras Coagulation disorders-joints and soft tissue Vascular disorders Loss of Integrity of blood vessels (increased vessel fragility and Purpura) Congenital vascular wall defects (Ehler-Danlos Syndrome) Acquired vascular purpura due to corticosteroid excess, purpura, immune complex deposition, scurvy Ehler-Danlos Syndrome) Platelet disorders Due to either 1. decrease in platelet number (thrombocytopenia) –congenital and acquired 2. Defective platelet function- inherited adhesion or aggregation defect OR acquired defect (Aspirin)  THORMBOCYTOPENIA Loss of platelets from the circulation faster than the rate of their production by the bone marrow. So thrombocytopenia is due to: A. Failure of platelets production, most common cause, Megakaryocytes are  in the bone marrow e.g. drugs. B.  rate of removal of platelets from the circulation. Megakaryocytes are  or normal in the bone marrow I.e production is normal but platelets are destroyed e.g. by antibodies.  Causes of Thrombocytopenia Congenital Acquired Megakaryocytic hypoplasia Immunothrombocytopenia ITP TAR syndrome Thrombotic thrombocytopenic purpura TTP Wiscott Aldrich syndrome DIC Drugs Infections Splenomegaly Bone marrow suppression or infiltration Aplastic anaemia  Idiopathic (immune) thrombocytopenic purpura (ITP) This is an autoimmune disorder with formation of antiplatelet antibodies, directed against membrane glycoproteins most often glycoprotein IIb-IIIa of platelets. The antiplatelet antibodies can be demonstrated in approximately 80% of patients and are of the IgG type. Pathogenesis of ITP: -IgG antibody attached to the red cell membrane. the antibody is directed against the glycoprotein(GP) IIb/IIIa or Ib complex. The mechanism of platelet destruction is similar to that seen in autoimmune hemolytic anemias. Platelet autoantibodies, usually IgG, result in the premature removal of platelets from the circulation by macrophages of the reticuloendothelial system, especially the spleen , The normal lifespan of a platelet is 10 days but in ITP this is reduced to a few hours. Total megakaryocyte mass and platelet turnover are increased in parallel to approximately five times normal. Etiology It is usually idiopathic but may be seen in association with other diseases such as systemic lupus erythematosus(SLE), human immunodefiency virus (HIV) infection, viral hepatitis, Helicobacter pylori infection, chronic lymphocytic leukaemia (CLL), Hodgkin lymphoma or autoimmune haemolytic anaemia Types of ITP -Acute ITP is a self-limited disease of children between 2 to 4 years. It often presents 1 to 3 weeks after viral (measles, rubella, EBV) infection or vaccination.The disease is usually self-limited and need no treatment. -Chronic ITP is defined as persistent thrombocytopenia lasting more than 6 to 12 months. This is more common in adults. Treatment usually needed. The highest incidence has been considered to be in women aged 15– 50 years Clinical features The onset is often insidious with petechial haemorrhage, easy bruising and, in women, menorrhagia. Mucosal bleeding (e.g.epistaxes or gum bleeding) occurs in severe cases but fortunately intracranial haemorrhage is rare. The severity of bleeding in ITP is usually less than that seen in patients with comparable degrees of thrombocytopenia from bone marrow failure;this is attributed to the circulation of predominantly young platelet Diagnosis of ITP: 1- The platelet count is low usually 10-50 x 109 /L. 2- The blood film shows reduced numbers of platelets 3- The bone marrow shows normal or increased numbers of megakaryocytes. 4- Platelets autoantibodies are positive. Treatment 1. Corticosteroids: Eighty per cent of patients remit on high- dose corticosteroid therapy. 2. High-dose intravenous immunoglobulin ;therapy is able to produce a rapid rise in platelet count in the majority of patients\ It is particularly useful in patients with life-threatening haemorrhage, in steroid-refractory ITP, during pregnancy or prior to surgery 3. Monoclonal antibody Rituximab (anti-CD20) produces responses in approximately 50%, 4. Immunosuppressive drugs 5. Thrombopoietin-receptor agonists 6. Splenectomy  Defective Platelets Function A defect in function is suspected if there is prolonged bleeding time with or without skin or mucosal hemorrhage in the presence of normal platelet count.  Disorders of Platelets Function Congenital Acquired Glanzman’s disease Drugs Uremia Bernard Soluier’s Myeloproliferative disorders Storage granules defect Multiple myeloma Test for platelet function 1. Platelet function analysis (PFA-100), 2. platelet aggregation studies and 3. VWF assays may be needed to diagnose platelet functional defects. Lab test for platelet disorder Bernard-Soulier Syndrome First recognized, in 1948, by two French hematologists Jean Bernard and JeanPierre Soulier. Autosomal recessive,usually with Adhesion defect. There is mild to moderate thrombocytopenia, and very large platelets(giant platelet ). presents early with bleeding symptoms—epistaxis, ecchymosis, menometrorrhagia, gingival and gastrointestinal bleeding Variable severity of symptoms May become less severe with age Glanzmann Thrombasthenia Platelet aggregation defective Platelet count and morphology are normal Inherited in autosomal recessive pattern Bleeding time is prolonged Consanguinity often noted Purpura and epistaxis are the in affected familie most frequent types of bleeding, Platelets are unable to especially in children aggregate Bleeding may decrease with age